Genetic variation of a heat shock transcription factor modulates cold tolerance in maize.

Understanding how maize (Zea mays L.) responds to cold stress is crucial for facilitating breeding programs of cold-tolerant varieties. Despite the extensive utilization of the genome-wide association study (GWAS) approach in exploring favorable natural alleles associated with maize cold tolerance, there are few reports that have successfully identified the candidate genes contributing to maize cold tolerance. In this study, by employing a diverse panel of maize inbred lines collected from different germplasm sources, we conducted a GWAS on the variation of the relative injured area of maize true leaves during cold stress-a trait most closely correlated with maize cold tolerance-and identified HSF21, encoding a B-class heat shock transcription factor, which positively regulates cold tolerance at both seedling and germination stages. The natural variations within the promoter of the cold-tolerant HSF21Hap1 allele led to increased HSF21 expression under cold stress by inhibiting the binding of bZIP68 transcription factor, a negative regulator of cold tolerance. Through integrated transcriptome deep sequencing, DNA affinity purification sequencing, and targeted lipidomic analysis, we unveiled the function of HSF21 in regulating lipid metabolism homeostasis for modulating cold tolerance in maize. Additionally, HSF21 confers maize cold tolerance without incurring yield penalties. This study thereby establishes HSF21 as a key regulator that enhances cold tolerance in maize, thus providing valuable genetic resources for the breeding of cold-tolerant maize varieties.

Pollution characteristics of heavy metals, antibiotic and antibiotic resistance genes in the crested ibis and their habitat across different lifestyle and geography.

Antibacterial resistance in wild animals has been increasingly reported worldwide, even though they are usually not directly exposed to clinically relevant antibiotics. Crested ibis, one of the rarest birds in the world, usually forages in paddy fields and prefer to nest and breed near villages that is greatly influenced by anthropogenic activities. We sampled the feces of crested ibises, as well as their habitat environment samples, to explore the pollution characteristics of heavy metals, antibiotics and antibiotic resistance genes (ARGs). Results showed that the pollution characteristics of heavy metals, antibiotic, ARGs and gut microbiota of crested ibis were more related by host lifestyle and habitats. Captive ibises had higher relative abundances of the total ARGs and tetracycline concentrations compared with feralization and wild ibises, while the heavy metal contents had shown the opposite result. The Characteristics of pollutants in the corresponding environmental samples also exhibited high similarity with the results of fecal samples. The relative abundances of Proteobacteria and Actinobacteria were significantly different between captive and wild individuals, while the abundance of majority bacterial genera was generally higher in wild populations. The concentrations of heavy metals in soil (Cd, Cu and Zn) and water (Cd, Cu, Zn and Cr) were both exceeded the background soil levels or surface water quality standards, suggesting multi-element contamination in the habitat. Ecological risk assessments of soils by Igeo and Er showed that the habitats of wild ibises were heavily and moderately contaminated by Cd, which would possibly pose a threat to the health of ibises. PLS-PM analysis indicated that microbial compositions and residual antibiotics had the most substantial impact on the dynamic changes in ARGs of ibis. Overall, this work provides a comprehensive understanding of the characteristics, risks of those contaminations, and their effects on the ARGs in the habitat of crested ibis.

Chromosome-specific painting reveals the Y genome origin and chromosome rearrangements of the St genome in Triticeae.

Karyotypes provide key cytogenetic information on phylogenetic relationships and evolutionary origins in related plant species. The St genome of Pseudoroegneria contributes to eight alloploid genera, representing over half of the species that are highly valuable for wheat (Triticum aestivum) breeding and for understanding Triticeae species evolution. However, St chromosome characterization is challenging due to limited cytogenetic markers and DNA information. We developed a complete set of St genome-specific chromosome painting probes for identification of the individual chromosomes 1St to 7St based on the genome sequences of Pse. libanotica and wheat. We revealed the conservation of St chromosomes in St-containing species by chromosome painting, including Pseudoroegneria, Roegneria, Elymus, and Campeiostachys. Notably, the Y genome showed hybridization signals, albeit weaker than those of the St genome. The awnless species harboring the Y genome exhibited more intense hybridization signals compare to the awned species in Roegneria and Campeiostachys, yet weaker than the hybridization signals of the St genome in autotetraploid Pse. strigosa. Although awnless species were morphologically more similar to each other, phenotypic divergence progressively increased from awnless to awned species. Our results indicate that the Y genome originated from the St genome and shed light on the possible origin of the Roegneria and Campeiostachys species, enhancing our understanding of St-genome-containing species evolution.

Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism.

The incidence rate of gestational diabetes mellitus (GDM) remains high among pregnant women in the second trimester of pregnancy. However, the main clinical approach to alleviate the symptoms of GDM is to control the diet. Our study explored the therapeutic effects of omega-3 fatty acids (ω-3 FAs) on GDM at the cellular and animal levels. We found that ω-3 FAs can promote the transformation of M0 macrophages into anti-inflammatory M2 macrophages. The transformed M2 macrophages promoted ß-oxidation and reduced hepatocyte lipid synthesis (P < 0.05), thereby promoting hepatic function and preventing the excessive accumulation of lipid droplets in the hepatocyte cell line HepG2. Supplementation of ω-3 FAs in pregnant GDM mice significantly reduced fasting blood glucose levels, glucose tolerance test, and insulin tolerance test indices, and lipid accumulation in the liver and effectively prevented the occurrence of liver fibrosis (P < 0.05). These therapeutic effects may be mediated through the anti-inflammatory effects of ω-3 FAs (P < 0.05). ω-3 FAs also had positive effects on the offspring of pregnant GDM mice, as demonstrated by reduced birth mortality and improved glycemic stabilization (P < 0.05). In conclusion, this study provides a possible translational medicine strategy for the treatment of GDM.

Development and characterization of defatted coconut flour based oleogels: A fat substitute for application in oil-fortified surimi.

This research examined the impact of defatted coconut flour (DCF)-based oleogels on the quality of surimi. Microscopic analysis indicated that the dietary fiber present in DCF could act as the main structure of the oleogels network. The formation of the oleogels network primarily relies on the tensile intramolecular or intermolecular hydrogen bonds between DCF and corn oil. The oleogels displayed oil binding capacity of up to 96.95% and exhibited favorable mechanical and rheological properties. Efforts were undertaken to integrate the acquired oleogels into silver carp surimi to create oil-fortified surimi products. Adding oleogels significantly enhanced the gel strength, texture, and water-holding capacity of surimi compared to adding corn oil. Especially, oleogels containing 5.0 % (w/v) DCF concentration elevated the lipid content in the surimi and preserved the gel and texture properties. Therefore, incorporating oleogels in surimi presents a potential solution for enhancing the nutritional content of surimi products.

Prognostic significance of copper metabolism-related genes as risk markers in bladder urothelial carcinoma.

Bladder urothelial carcinoma (BLCA), a prevalent malignant neoplasm affecting the human urinary system, is frequently linked with an unfavorable prognosis in a significant proportion of individuals. More effective and sensitive markers are needed to provide a reference for prognostic judgment. We obtained RNA sequencing data and clinical information of individuals from TCGA, and 133 copper metabolism-related genes from literature. Prognostic genes were evaluated by univariate/multivariate Cox regression analysis and LASSO analysis, and a risk-scoring model was established and validated in the GEO dataset. The CIBERSORT method was utilized to explore immune cell infiltration in BLCA individuals. In addition, tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) were utilized to verify whether the model can foretell the response of BLCA individuals to immunotherapy. We successfully constructed an 8-gene risk scoring model to foretell individuals' overall survival, and the model performed well in TCGA training and GEO validation cohorts. Lastly, a nomogram containing clinical parameters and risk scores was constructed to help individualized result prediction for individuals. Calibration curves demonstrated a high degree of concordance between the observed and projected survival durations, attesting to its exceptional predictive accuracy. Analysis utilizing CIBERSORT unveiled elevated levels of immune cell infiltration in individuals classified as low risk. TIDE and IPS analyses substantiated that low-risk individuals exhibited a more favorable response to immunotherapy. In summary, the model held immense potential for stratifying the risk of survival and guiding tailored treatment approaches for individuals with BLCA, thereby offering valuable insights for personalized therapeutic interventions.

Effects of storm events on nutrient characteristics in a stratified drinking water reservoir: Behavior, transmission pathways and management strategy.

Storm events result in nutrient fluctuations and deterioration of reservoir water supply quality. Understanding of nutrient dynamics (e.g., concentration, composition, loads and transport pathways) and adoption of effective management strategies are critical for safeguarding water quality. A comprehensive monitoring was conducted for three storm events during the rainy season in 2023. Results showed nitrogen (N) and phosphorus (P) dynamics demonstrate a significant response to hydrological process. Rainfall resulted in the highest event mean concentrations (EMCs) of total nitrogen (TN), nitrate nitrogen (NO3--N), ammonia nitrogen (NH4+-N), total phosphorus (TP), and particulate phosphorus (PP) in the runoff being 1.97, 2.15, 2.30, 44.17, and 62.38 times higher than those observed in baseflow. On average, NO3--N/PP accounted for 82 %/96 % of N/P exports. Hysteresis analyses reveal that NH4+-N and PP were mainly transported by surface runoff from over-land sources, whereas TN and NO3--N were primarily delivered by subsurface runoff. Additionally, nutrient concentrations were significantly higher in the intrusive layer in reservoir compared to the pre-storm period, which gradually decreased from the tail to the head as particulate sedimentation and water column mixing occurred. Water-lifting-aerators (WLAs) were employed to alter the reservoir thermal stratification regime via artificial mixing to affect the intrusive layer of storm runoff. Comparison of the intrusive layer for three storms reveals that WLAs triggers the storm runoff to form an underflow via increasing the reservoir bottom water temperature above that the runoff, ensuring that water quality at the intake position remains unaffected by inflows. These findings serve as a reference for the response of reservoir eutrophication levels to storm events and present practical engineering experience for enhancing water quality safety during the rainy season.

Prophylactic supplementation with Bifidobacterium infantis or its metabolite inosine attenuates cardiac ischemia/reperfusion injury.

Emerging evidence has demonstrated the profound impact of the gut microbiome on cardiovascular diseases through the production of diverse metabolites. Using an animal model of myocardial ischemia-reperfusion (I/R) injury, we found that the prophylactic administration of a well-known probiotic, Bifidobacterium infantis (B. infantis), exhibited cardioprotective effects in terms of preserving cardiac contractile function and preventing adverse cardiac remodeling following I/R and that these cardioprotective effects were recapitulated by its metabolite inosine. Transcriptomic analysis further revealed that inosine mitigated I/R-induced cardiac inflammation and cell death. Mechanistic investigations elucidated that inosine suppressed the production of pro-inflammatory cytokines and reduced the numbers of dendritic cells and natural killer cells, achieved through the activation of the adenosine A2A receptor (A2AR) that when inhibited abrogated the cardioprotective effects of inosine. Additionally, in vitro studies using C2C12 myoblasts revealed that inosine attenuated cell death by serving as an alternative carbon source for adenosine triphosphate (ATP) generation through the purine salvage pathway when subjected to oxygen-glucose deprivation/reoxygenation that simulated myocardial I/R injury. Likewise, inosine reversed the I/R-induced decrease in ATP levels in mouse hearts. Taken together, our findings indicate that B. infantis or its metabolite inosine exerts cardioprotective effects against I/R by suppressing cardiac inflammation and attenuating cardiac cell death, suggesting prophylactic therapeutic options for acute ischemic cardiac injury.

Timing offset calibration for TOF PET using stationary line source scans at multiple positions.

Background. Accurate timing offset calibration is crucial for time-of-flight (TOF) positron emission tomography (PET) to mitigate image artifacts and improve quantitative accuracy. However, existing methods are often time-consuming, complex, or costly.Objective. This paper presents a method for TOF PET timing offset calibration that eliminates the need for costly equipment, phantoms, short-half-life sources, and precise source positioning.Approach. We estimate channel timing offsets using stationary scans of a68Ge line source, typically used for routine quality control, at a minimum of three non-coplanar positions, with each position scanned for two minutes. The line source positions are determined accurately from reconstructed images using a simple algorithm, allowing precise calculation of arrival time differences. Channel timing offsets are estimated by solving a least squares problem. This method is assessed through analyses of phantoms and patient images using a RAYSOLUTION DigitMI 930 scanner.Main results. The estimated timing offsets ranged from -500 ps to 500 ps across all channels. Calibration with a minimum of three scanned positions was sufficient to correct these offsets, achieving less than a 1% discrepancy across various metrics of the image quality (IQ) phantom compared to 12 positions. This calibration significantly reduced edge artifacts in TOF reconstruction of both phantoms and patients. Furthermore, the IQ phantom displayed a 13% increase in average contrast recovery (CR), a 68% reduction in average background variability (BV) across all spheres, and an 80% reduction in average residual error. Consistent with the phantom results, patient data revealed enhancements in maximum standardized uptake values (SUVmax) from 14% to 55% for lesions measuring 6 mm to 14 mm. The calibration also improved lesion-to-background contrast and eliminated artifacts caused by the spillover effect of the kidneys and bladder.Significance. The proposed method is fast, user-friendly, and cost-effective, effectively improving lesion detection and diagnostic accuracy.

Fibrin-konjac glucomannan-black phosphorus hydrogel scaffolds loaded with nasal ectodermal mesenchymal stem cells accelerated alveolar bone regeneration.

BACKGROUND: Effective treatments for the alveolar bone defect remain a major concern in dental therapy. The objectives of this study were to develop a fibrin and konjac glucomannan (KGM) composite hydrogel as scaffolds for the osteogenesis of nasal mucosa-derived ectodermal mesenchymal stem cells (EMSCs) for the regeneration of alveolar bone defect, and to investigate the osteogenesis-accelerating effects of black phosphorus nanoparticles (BPNs) embedded in the hydrogels. METHODS: Primary EMSCs were isolated from rat nasal mucosa and used for the alveolar bone recovery. Fibrin and KGM were prepared in different ratios for osteomimetic hydrogel scaffolds, and the optimal ratio was determined by mechanical properties and biocompatibility analysis. Then, the optimal hydrogels were integrated with BPNs to obtain BPNs/fibrin-KGM hydrogels, and the effects on osteogenic EMSCs in vitro were evaluated. To explore the osteogenesis-enhancing effects of hydrogels in vivo, the BPNs/fibrin-KGM scaffolds combined with EMSCs were implanted to a rat model of alveolar bone defect. Micro-computed tomography (CT), histological examination, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were conducted to evaluate the bone morphology and expression of osteogenesis-related genes of the bone regeneration. RESULTS: The addition of KGM improved the mechanical properties and biodegradation characteristics of the fibrin hydrogels. In vitro, the BPNs-containing compound hydrogel was proved to be biocompatible and capable of enhancing the osteogenesis of EMSCs by upregulating the mineralization and the activity of alkaline phosphatase. In vivo, the micro-CT analysis and histological evaluation demonstrated that rats implanted EMSCs-BPNs/fibrin-KGM hydrogels exhibited the best bone reconstruction. And compared to the model group, the expression of osteogenesis genes including osteopontin (Opn, p < 0.0001), osteocalcin (Ocn, p < 0.0001), type collagen (Col , p < 0.0001), bone morphogenetic protein-2 (Bmp2, p < 0.0001), Smad1 (p = 0.0006), and runt-related transcription factor 2 (Runx2, p < 0.0001) were all significantly upregulated. CONCLUSIONS: EMSCs/BPNs-containing fibrin-KGM hydrogels accelerated the recovery of the alveolar bone defect in rats by effectively up-regulating the expression of osteogenesis-related genes, promoting the formation and mineralisation of bone matrix.

Liver-Targeted Nanoparticles Loaded with Cannabidiol Based on Redox Response for Effective Alleviation of Acute Liver Injury.

The purpose of this work was to construct liver-targeted nanoparticles based on the redox response to effectively deliver cannabidiol (CBD) for the prevention of acute liver injury (ALI). CBD-loaded nanoparticles (CBD NPs) with a particle size of 126.5 ± 1.56 nm were prepared using the polymer DA-PP-LA obtained by grafting pullulan polysaccharide with deoxycholic acid (DA) and α-lipoic acid (α-LA). CBD NPs showed typical redox-response release behavior. Interestingly, CBD NPs exhibited admirable liver targeting ability, significantly accumulated in the liver, and effectively promoted the internalization of CBD in liver cells, thus effectively reducing the H2O2-induced oxidative damage of HepG2 cells and avoiding apoptosis. More importantly, CBD NPs effectively prevented CCl4-induced ALI by protecting liver function, ameliorating oxidative stress levels, inhibiting the production of inflammatory factors, and protecting the liver from histological damage. This study provides a promising strategy for achieving targeted delivery of CBD NPs in the liver, thereby effectively preventing ALI.

Deep Learning-Based Defects Detection in Keyhole TIG Welding with Enhanced Vision.

Keyhole tungsten inert gas (keyhole TIG) welding is renowned for its advanced efficiency, necessitating a real-time defect detection method that integrates deep learning and enhanced vision techniques. This study employs a multi-layer deep neural network trained on an extensive welding image dataset. Neural networks can capture complex nonlinear relationships through multi-layer transformations without manual feature selection. Conversely, the nonlinear modeling ability of support vector machines (SVM) is limited by manually selected kernel functions and parameters, resulting in poor performance for recognizing burn-through and good welds images. SVMs handle only lower-level features such as porosity and excel only in detecting simple edges and shapes. However, neural networks excel in processing deep feature maps of "molten pools" and can encode deep defects that are often confused in keyhole TIG. Applying a four-class classification task to weld pool images, the neural network adeptly distinguishes various weld states, including good welds, burn-through, partial penetration, and undercut. Experimental results demonstrate high accuracy and real-time performance. A comprehensive dataset, prepared through meticulous preprocessing and augmentation, ensures reliable results. This method provides an effective solution for quality control and defect prevention in keyhole TIG welding process.

The gut microbiota-oligodendrocyte axis: A promising pathway for modulating oligodendrocyte homeostasis and demyelination-associated disorders.

The bidirectional regulation between the gut microbiota and brain, known as gut-brain axis, has received significant attention. The myelin sheath, produced by oligodendrocytes or Schwann cells, is essential for efficient nervous signal transmission and the maintenance of brain function. Growing evidence shows that both oligodendrogenesis and myelination are modulated by gut microbiota and its metabolites, and when dysbiosis occurs, changes in the microbiota composition and/or associated metabolites may impact developmental myelination and the occurrence of neurodevelopmental disabilities. Although the link between the microbiota and demyelinating disease such as multiple sclerosis has been extensively studied, our knowledge about the role of the microbiota in other myelin-related disorders, such as neurodegenerative diseases, is limited. Mechanistically, the microbiota-oligodendrocyte axis is primarily mediated by factors such as inflammation, the vagus nerve, endocrine hormones, and microbiota metabolites as evidenced by metagenomics, metabolomics, vagotomy, and morphological and molecular approaches. Treatments targeting this axis include probiotics, prebiotics, microbial metabolites, herbal bioactive compounds, and specific dietary management. In addition to the commonly used approaches, viral vector-mediated tracing and gene manipulation, integrated multiomics and multicenter clinical trials will greatly promote the mechanistic and interventional studies and ultimately, the development of new preventive and therapeutic strategies against gut-oligodendrocyte axis-mediated brain impairments. Interestingly, recent findings showed that microbiota dysbiosis can be induced by hippocampal myelin damage and is reversible by myelin-targeted drugs, which provides new insights into understanding how hippocampus-based functional impairment (such as in neurodegenerative Alzheimer's disease) regulates the peripheral homeostasis of microbiota and associated systemic disorders.

Expression and clinical significance of U2AF homology motif kinase 1 in oral squamous cell carcinoma.

OBJECTIVE: U2AF homology motif kinase 1 (UHMK1) is a newly discovered molecule that may have multiple functions. Recent studies have revealed that UHMK1 had aberrant expression in many tumors and was associated with tumor progression. However, UHMK1 was rarely reported in oral squamous cell carcinoma (OSCC). STUDY DESIGN: In this study, Western blot, quantitative real-time polymerase chain reaction (PCR), and immunohistochemistry were used to detect the expression of UHMK1 in OSCC and peritumoral non-neoplastic tissues. Then, its relationship with clinicopathologic parameters was analyzed. The Kaplan-Meier method and Cox regression model were used to analyze the effects of UHMK1 expression on the prognosis and survival of OSCC patients. RESULTS: Our results showed that UHMK1 had higher expression in OSCC tissues compared with in peritumoral non-neoplastic tissues, and its high expression was associated with high TNM stage and lymph node metastasis. High UHMK1 expression was related to short overall and disease-free survival times. Moreover, UHMK1 expression was identified as an independent prognostic factor that influences overall and disease-free survival of OSCC patients. CONCLUSIONS: High expression of UHMK1 is associated with the poor prognosis of patients, and it can be used as a potential prognostic molecule for OSCC.

Suboptimal reporting of randomized controlled trials on non-pharmacological therapies in Chinese medicine.

With the successive release of the CONSORT extensions for acupuncture, moxibustion, cupping, and Tuina/massage, this review aims to assess the reporting characteristics and quality of randomized controlled trials (RCTs) based on these specific guidelines. A comprehensive review was conducted by searching multiple databases, including Embase, Ovid MEDLINE(R), All EBM Reviews, AMED, CNKI, VIP Chinese Medical Journal Database, and Wanfang Data, for publications from January 1 to December 31, 2022. Two reviewers independently evaluated the eligibility of the records, extracted predetermined information, and assessed the reporting based on the STRICTA, STRICTOM, STRICTOC, and STRICTOTM checklists. Among the included 387 studies (acupuncture, 213; Tuina/massage, 85; moxibustion, 73; cupping, 16), the overall reporting compliance averaged 56.0%, with acupuncture leading at 62.6%, followed by cupping (60.2%), moxibustion (53.1%), and Tuina/massage (47.9%). About half of the evaluated items showed poor reporting (compliance rate < 65%). Notably, international journals demonstrated significantly higher reporting quality than Chinese journals (P < 0.05). Although acupuncture trials had relatively higher compliance rates, deficiencies persist in reporting non-pharmacological therapies of Chinese medicine, particularly in areas like treatment environment details and provider background information.

Multiplex Sensing of Biomarkers on the Cancer Cell Surface by an Epithelial-Mesenchymal Transition (EMT) Sensing Panel Enables Precise Differentiating of Cancer Cells at Various EMT Stages.

Epithelial-mesenchymal transition (EMT) is a complex process that plays a critical role in tumor progression. In this study, we present an EMT sensing panel for the classification of cancer cells at different EMT stages. This sensing panel consists of three types of fluorescent probes based on boronic acid-functionalized carbon-nitride nanosheet (BCN) derivatives. The selective response toward different EMT-associated biomarkers, namely, EpCAM, N-cadherin, and sialic acid (SA), was achieved by conjugating the corresponding antibodies to each BCN derivative, whereas the rare-earth-doping ensures simultaneous sensing of the three biomarkers with fluorescent emission of the three probes at different wavelengths. Sensitive sensing of the three biomarkers was achieved at the protein level with LODs reaching 1.35 ng mL-1 for EpCAM, 1.62 ng mL-1 for N-cadherin, and 1.54 ng mL-1 for SA. The selective response of these biomarkers on the cell surface also facilitated sensitive detection of MCF-7 cells and MDA-MB-231 cells with LODs of 2 cells/mL and 2 cells/mL, respectively. Based on the simultaneous sensing of the three biomarkers on cancer cells that underwent different extents of EMT, precise discrimination and classification of cells at various EMT stages were also achieved with an accuracy of 93.3%. This EMT sensing panel provided a versatile tool for monitoring the EMT evolution process and has the potential to be used for the evaluation of the EMT-targeting therapy and metastasis prediction.

Jianpi Huayu Prescription Prevents Atherosclerosis by Improving Inflammation and Reshaping the Intestinal Microbiota in ApoE-/- Mice.

This study established an LPS-induced RAW264.7 macrophage inflammatory injury model and an AS mouse vulnerable plaque model to observe the effect of JPHYP on macrophage inflammation, plaque formation, blood lipids, inflammation levels, intestinal flora and the influence of TLR4/MyD88/MAPK pathway, and explore the anti-AS effect and molecular mechanism of JPHYP, and detected 16S rRNA of mice intestinal microbes. The difference of intestinal flora in different groups of mice was compared to further explore the intervention effect of JPHYP and clarify the molecular biological mechanism of JPHYP in preventing and treating AS by regulating TLR4/MyD88/MAPK inflammatory signaling pathway and improving intestinal flora.

Matrix stiffness-dependent PD-L2 deficiency improves SMYD3/xCT-mediated ferroptosis and the efficacy of anti-PD-1 in HCC.

INTRODUCTION: Heterogeneous tissue stiffening promotes tumor progression and resistance, and predicts a poor clinical outcome in patients with hepatocellular carcinoma (HCC). Ferroptosis, a congenital tumor suppressive mechanism, mediates the anticancer activity of various tumor suppressors, including immune checkpoint inhibitors, and its induction is currently considered a promising treatment strategy. However, the role of extracellular matrix (ECM) stiffness in regulating ferroptosis and ferroptosis-targeted resistance in HCC remains unclear. OBJECTIVES: This research aimed to explore how extracellular matrix stiffness affects ferroptosis and its treatment efficacy in HCC. METHODS: Ferroptosis analysis was confirmed via cell activity, intracellular ferrous irons, and mitochondrial pathology assays. Baseline PD-L2, SMYD3, and SLC7A11 (xCT) were evaluated in 67 sorafenib-treated patients with HCC (46 for non-responder and 21 for responder) from public data. The combined efficacy of shPD-L2, sorafenib, and anti-PD-1 antibody in HCC was investigated in vivo. RESULTS: Here, we revealed that matrix stiffness-induced PD-L2 functions as a suppressor of xCT-mediated ferroptosis to promote cancer growth and sorafenib resistance in patients with HCC. Mechanically, matrix stiffening induced the expression of PD-L2 by activating SMYD3/H3K4me3, which acts as an RNA binding protein to enhance the mRNA stability of FTL and elevate its protein level. Knockdown of PD-L2 significantly promoted xCT-mediated ferroptosis induced by RSL3 or sorafenib on stiff substrate via FTL, whereas its overexpression abolished these upward trends. Notably, PD-L2 deletion in combination with sorafenib and anti-PD-1 antibody significantly sensitized HCC cells and blunted cancer growth in vivo. Additionally, we found the ferroptosis- and immune checkpoint-related prognostic genes that combined PD-L2, SLC7A11 and SYMD3 well predict the clinical efficacy of sorafenib in patients with HCC. CONCLUSION: These findings expand our understanding of the mechanics-dependent PD-L2 role in ferroptosis, cancer progression and resistance, providing a basis for the clinical translation of PD-L2 as a therapeutic target or diagnostic biomarker.

Starch-based self-assembled three-dimensional network nanostructure materials for sustainable cascade adsorption.

Toward the development of a sustainable utilization strategy for adsorption materials, a starch-based adsorbent starch-chitosan-tannic acid (St-CTS-TA) with a three-dimensional (3D) structure was fabricated in water via electrostatic and hydrogen bonding reactions between St, CTS, and TA without using toxic reducing agents or special instruments. St-CTS-TA demonstrated a high specific surface area of 37 m2/g as well as a mesoporous/macroporous distribution ranging from 30 to 80 nm, which enhanced the mass transfer of adsorbate and the exposure of catechol groups in TA. The Langmuir isotherm adsorption model revealed that the highest adsorption capacities of St-CTS-TA for Fe3+ and Co2+ were 1678.2 and 944.8 mg/g, respectively. Surprisingly, the specific surface area of St-CTS-TA increased from 37 to 87 and 42 m2/g after Fe3+ and Co2+ adsorption, respectively, and the resulting St-CTS-TA-Fe and St-CTS-TA-Co could continuously adsorb basic fuchsin (BF) and rhodamine B (RhB). The adsorption capacities of St-CTS-TA-Fe and St-CTS-TA-Co for BF/RhB were found to be 1854.79/401.19 mg/g and 2229.77/537.49 mg/g, respectively, based on the Langmuir isotherm adsorption model.

Clinical characterization and long-term postoperative outcomes of retinoblastoma patients receiving enucleation and primary orbital implantation in early infancy: an observational study.

OBJECTIVES: To retrospectively investigate clinical characterization and the long-term postoperative outcomes of retinoblastoma (RB) patients receiving enucleation with primary orbital implantation in early infancy (0-6 months old). METHODS: The clinical and follow-up data of 42 RB patients receiving enucleation with primary orbital implantation in early infancy at Beijing Tongren Hospital from December 2009 to January 2020 were analysed. The average follow-up time was 83 months. The patient group included 24 males and 18 females, 30 unilateral and 12 bilateral cases. A total of 44 eyes with 10 in stage D and 34 in stage E underwent 40 unilateral and 2 bilateral surgeries. 17 RB eyes received hydrogel and 27 RB eyes received hydroxyapatite implants. This study was performed by following the guideline of STROBE. RESULTS: Enucleation combined with primary orbital implantation promoted survival and was safe with few and minor complications such as increased secretion, upper eyelid ptosis, and sunken eye sockets which were not affected by stages, lateralities, or implant materials. 55-80% RB patients exhibited satisfactory appearance and obvious or moderate motility of orbital implants according to the evaluation by doctors and family members. Family members were likely more optimistic about the appearance and more pessimistic about motility of the orbital implantation than doctors did.The quality of life was high as indicated by PedsQL3.0 or PedsQL4.0 scores ( ≧ 90 for > 75% patients). It was not affected by the stages, laterality, and implant materials, nor affected by the appearance and motility of the implants. CONCLUSIONS: The outcomes of the combination of enucleation and primary orbital implantation for pertinent RB patients in early infancy are generally satisfactory with few and minor complications, high safety, appearance, and overall quality of life. Enucleation combined with primary orbital implantation in early infancy benefits pertinent RB patients in appearance, survival, and quality of life.