Enhancing osteogenesis and angiogenesis functions for Ti-24Nb-4Zr-8Sn scaffolds with methacrylated gelatin and deferoxamine.

Repair of large bone defects remains challenge for orthopedic clinical treatment. Porous titanium alloys have been widely fabricated by the additive manufacturing, which possess the elastic modulus close to that of human cortical bone, good osteoconductivity and osteointegration. However, insufficient bone regeneration and vascularization inside the porous titanium scaffolds severely limit their capability for repair of large-size bone defects. Therefore, it is crucially important to improve the osteogenic function and vascularization of the titanium scaffolds. Herein, methacrylated gelatin (GelMA) were incorporated with the porous Ti-24Nb-4Zr-8Sn (Ti2448) scaffolds prepared by the electron beam melting (EBM) method (Ti2448-GelMA). Besides, the deferoxamine (DFO) as an angiogenic agent was doped into the Ti2448-GelMA scaffold (Ti2448-GelMA/DFO), in order to promote vascularization. The results indicate that GelMA can fully infiltrate into the pores of Ti2448 scaffolds with porous cross-linked network (average pore size: 120.2 ± 25.1 µm). Ti2448-GelMA scaffolds facilitated the differentiation of MC3T3-E1 cells by promoting the ALP expression and mineralization, with the amount of calcium contents ∼2.5 times at day 14, compared with the Ti2448 scaffolds. Impressively, the number of vascular meshes for the Ti2448-GelMA/DFO group (∼7.2/mm2) was significantly higher than the control group (∼5.3/mm2) after cultivation for 9 h, demonstrating the excellent angiogenesis ability. The Ti2448-GelMA/DFO scaffolds also exhibited sustained release of DFO, with a cumulative release of 82.3% after 28 days. Therefore, Ti2448-GelMA/DFO scaffolds likely provide a new strategy to improve the osteogenesis and angiogenesis for repair of large bone defects.

Predictive value of bronchoscopy combined with CT score for refractory mycoplasma pneumoniae pneumonia in children.

INTRODUCTION: Mycoplasma pneumoniae pneumonia (MPP) is prevalent in paediatric patients and can progress to refractory mycoplasma pneumoniae pneumonia (RMPP). OBJECTIVE: To assess the predictive value of bronchoscopy combined with computed tomography (CT) score in identifying RMPP in children. METHODS: A retrospective analysis was conducted on 244 paediatric patients with MP, categorising them into RMPP and general mycoplasma pneumoniae pneumonia (GMPP) groups. A paired t-test compared the bronchitis score (BS) and CT score before and after treatment, supplemented by receiver operating characteristic (ROC) analysis. RESULTS: The RMPP group showed higher incidences of extrapulmonary complications and pleural effusion (58.10% and 40%, respectively) compared with the GMPP group (44.60%, p = 0.037 and 18.71%, p < 0.001, respectively). The CT scores for each lung lobe were statistically significant between the groups, except for the right upper lobe (p < 0.05). Correlation analysis between the total CT score and total BS yielded r = 0.346 and p < 0.001. The ROC for BS combined with CT score, including area under the curve, sensitivity, specificity, and cut-off values, were 0.82, 0.89, 0.64, and 0.53, respectively. CONCLUSION: The combined BS and CT score method is highly valuable in identifying RMPP in children.

A nomogram for predicting postoperative delirium in pediatric patients following cardiopulmonary bypass: A prospective observational study.

OBJECTIVES: To create a nomogram for early delirium detection in pediatric patients following cardiopulmonary bypass. RESEARCH METHODOLOGY/DESIGN: This prospective, observational study was conducted in the Cardiac Intensive Care Unit at a Children's Hospital, enrolling 501 pediatric patients from February 2022 to January 2023. Perioperative data were systematically collected through the hospital information system. Postoperative delirium was assessed using the Cornell Assessment of Pediatric Delirium (CAPD). For model development, Least Absolute Shrinkage and Selection Operator (LASSO) regression was employed to identify the most relevant predictors. These selected predictors were then incorporated into a multivariable logistic regression model to construct the predictive nomogram. The performance of the model was evaluated by Harrell's concordance index, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. External validity of the model was confirmed through the C-index and calibration plots. RESULTS: Five independent predictors were identified: age, SpO2 levels, lymphocyte count, diuretic use, and midazolam administration, integrated into a predictive nomogram. This nomogram demonstrated strong predictive capacity (AUC 0.816, concordance index 0.815) with good model fit (Hosmer-Lemeshow test p = 0.826) and high accuracy. Decision curve analysis showed a significant net benefit, and external validation confirmed the nomogram's reliability. CONCLUSIONS: The study successfully developed a precise and effective nomogram for identifying pediatric patients at high risk of post-cardiopulmonary bypass delirium, incorporating age, SpO2 levels, lymphocyte counts, diuretic use, and midazolam medication. IMPLICATIONS FOR CLINICAL PRACTICE: This nomogram aids early delirium detection and prevention in critically ill children, improving clinical decisions and treatment optimization. It enables precise monitoring and tailored medication strategies, significantly contributes to reducing the incidence of delirium, thereby enhancing the overall quality of patient care.

Transformation of Coherent Twin Boundary into Basal-Prismatic Boundary in HCP-Ti: A Molecular Dynamics Study.

The manufacturing process for wrought Ti alloys with the hexagonal close-packed (HCP) structure introduces a complicated microstructure with abundant intra- and inter-grain boundaries, which greatly influence performance. In the hexagonal close-packed (HCP) structure, two types of grain boundaries are commonly observed between grains with ~90° misorientation: the basal/prismatic boundary (BPB) and the coherent twin boundary (CTB). The mechanical response of the BPB and CTB under external loading was studied through molecular dynamic simulations of HCP-Ti. The results revealed that CTB undergoes transformation into BPB through the accumulation of twin boundary (TB) steps and subsequent emission of Shockley partial dislocations. When the total mismatch vector is close to the Burgers vector of a Shockley partial dislocation, BPB emits partial dislocations and further grows along the stacking faults. When a pair of CTBs are close to each other, severe boundary distortion occurs, facilitating the emission and absorption of partial dislocations, which further assists the CTB-BPB transformation. The present results thus help to explain the frequent observation of coexisting CTB and BPB in HCP alloys and further contribute to the understanding of their microstructure and property regulation.

Design, synthesis and biological evaluation of 4-(indolin-1-yl)-6-substituted-pyrido[3,2-d]pyrimidine derivatives as Mnk1/2 inhibitors.

The Mnk-eIF4E axis plays a crucial role in tumor development, and inhibiting Mnk kinases is a promising approach for cancer therapy. Starting with fragment WS23, a series of 4-(indolin-1-yl)-6-substituted-pyrido[3,2-d]pyrimidine derivatives were designed and synthesized. Among these derivatives, compound 15b showed the highest potency with IC50 values of 0.8 and 1.5 nM against Mnk1 and Mnk2, respectively. Additionally, it demonstrated good selectivity among 30 selected kinases. 15b significantly suppressed MOLM-13 and K562 cell lines growth and caused cell cycle arrest. Furthermore, the Western blot assay revealed that 15b effectively downregulated the downstream proteins p-eIF4E, Mcl-1, and c-myc. Additionally, 15b exhibited remarkable stability in rat plasma and rat and human microsomes. In vivo anti-tumor activity study suggested that treatment with 15b suppressed tumor growth in LL/2 syngeneic models. These findings highlight the potential of 15b as a novel and potent Mnks inhibitor, which deserves further investigation.

Essential role of glycoprotein Ibα in platelet activation.

Glycoprotein (GP) Ib, the ligand-binding subunit of platelet GPIb-IX complex, interacts with von Willebrand factor (VWF) exposed at the injured vessel wall, initiating platelet adhesion, activation, hemostasis, and thrombus formation. The cytoplasmic tail of GPIb interacts with 14-3-3, regulate ng the VWF-GPIb-elicited signal transduction and VWF binding function of GPIb. However, we unexpectedly found that the GPIb-14-3-3 association, beyond VWF-dependent function, is essential for general platelet activation. We found that the GPIb cytoplasmic tail peptide MPC, a potential GPIb inhibitor, by itself induced platelet aggregation, integrin αIIbß3 activation, granule secretion, and phosphatidylserine (PS) exposure. Conversely, the deletion of the cytoplasmic tail of GPIb in mouse platelets (10aa-/-) decreased platelet aggregation, integrin IIb3 activation, granule secretion, and PS exposure induced by various physiological agonists. Phosphoproteome-based kinase activity profiling revealed significantly upregulated protein kinase C (PKC) activity in MPC-treated platelets. MPC-induced platelet activation was abolished by the pan-PKC inhibitor and PKC deletion. Decreased PKC activity was observed in both resting and agonist-stimulated 10aa-/- platelets. GPIb regulates PKC activity by sequestering 14-3-3 from PKC. In vivo, the deletion of the GPIb cytoplasmic tail impaired mouse hemostasis and thrombus formation and protected against platelet-dependent pulmonary thromboembolism. Therefore, our findings demonstrate an essential role for the GPIb cytoplasmic tail in regulating platelet general activation and thrombus formation beyond the VWF-GPIb axis.

Analytical validation of the DropXpert S6 system for diagnosis of chronic myelocytic leukemia.

Digital PCR is a powerful method for absolute nucleic acid quantification and is widely used in the absolute quantification of viral copy numbers, tumor marker detection, and prenatal diagnosis. However, for most of the existing droplet-based dPCR systems, the droplet generation, PCR reaction, and droplet detection are performed separately using different instruments. Making digital PCR both easy to use and practical by integrating the qPCR workflow into a superior all-in-one walkaway solution is one of the core ideas. A new innovative and integrated digital droplet PCR platform was developed that utilizes cutting-edge microfluidics to integrate dPCR workflows onto a single consumable chip. This makes previously complex workflows fast and simple; the whole process of droplet generation, PCR amplification, and droplet detection is completed on one chip, which meets the clinical requirement of "sample in, result out". It provides high multiplexing capabilities and strong sensitivity while all measurements were within the 95% confidence interval. This study is the first validation of the DropXpert S6 system and focuses primarily on verifying its reliability, repeatability, and consistency. In addition, the accuracy, detection limit, linearity, and precision of the system were evaluated after sample collection. Among them, the accuracy assessment by calculating the absolute bias of each target gene yielded a range from -0.1 to 0.08, all within ±0.5 logarithmic orders of magnitude; the LOB for the assay was set at 0, and the LoD value calculated using probit curves is MR4.7 (0.002%); the linearity evaluation showed that the R2 value of the BCR-ABL was 0.9996, and the R2 value of the ABL metrics calculated using the ERM standard was 0.9999; and the precision evaluation showed that all samples had a CV of less than 4% for intra-day, inter-day, and inter-instrument variation. The CV of inter-batch variation was less than 7%. The total CV was less than 5%. The results of the study demonstrate that dd-PCR can be applied to molecular detection and the clinical evaluation of CML patients and provide more precise personal treatment guidance, and its reproducibility predicts the future development of a wide range of clinical applications.

Antimicrobial and hydrophobic cellulose paper prepared by covalently attaching cinnamaldehyde for strawberries preservation.

The demand for paper-based packaging materials as an alternative to incumbent disposable petroleum-derived polymers for food packaging applications is ever-growing. However, typical paper-based formats are not suitable for use in unconventional applications due to inherent limitations (e.g., excessive hydrophilicity, lack antimicrobial ability), and accordingly, enabling new capabilities is necessity. Herein, a simple and environmentally friendly strategy was proposed to introduce antimicrobial and hydrophobic functions to cellulose paper through successive chemical grafting of 3-aminopropyltriethoxysilane (APS) and cinnamaldehyde (CA). The results revealed that cellulose paper not only showed long-term antibacterial effect on different bacteria, but also inhibited a wide range of fungi. Encouragingly, the modified paper, which is fluorine-free, displays a high contact angle of 119.7°. Thus, even in the wet state, the modified paper can still maintain good mechanical strength. Meanwhile, the multifunctional composite papers have excellent biocompatibility and biodegradability. Compared with ordinary cellulose paper, multifunctional composite paper can effectively prolong the shelf life of strawberries. Therefore, the multifunctional composite paper represents good application potential as a fruit packaging material.

Type I Photoinitiator Based on Sustainable Carbon Dots.

Sustainable carbon dots comprising surficial oxime ester groups following homolytic bond cleavage exhibit potential as photoinitiators for traditional free radical photopolymerization. Carbon dots were made following a solvothermal procedure from sustainable furfural available from lignocellulose. Surficial aldehyde moieties reacted with hydroxylamine to the respective oxime while reaction with benzoyl chloride resulted in a biobased Type I photoinitiator comprising sustainable carbon dot (CD-PI). Photoinitiating ability was compared with the traditional photoinitiator (PI) ethyl (2,4,6-trimethyl benzoyl) phenyl phosphinate (TPO-L) by real-time FTIR with UV exposure at 365 nm. Photopolymer composition based on a mixture of urethane dimethacrylate (UDMA) and tripropylene glycol diethacrylate (TPGDA) resulted in a similar final conversion of about 70% using either CD-PI or TPO-L. Nevertheless, it appeared homogeneous in the case of compositions processed with CD-PI, while those made with TPO-L were heterogeneous as shown by two glass transition temperatures. Moreover, the migration rate of CD-PI in the cured samples was lower in comparison with those samples using TPO-L as PI.

Identifying an immunogenic cell death-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma.

BACKGROUND: Immunogenic cell death (ICD) is a regulated form of cell death that triggers an adaptive immune response. The objective of this study was to investigate the correlation between ICD-related genes (ICDGs) and the prognosis and the immune microenvironment of patients with lung adenocarcinoma (LUAD). METHODS: ICD-associated molecular subtypes were identified through consensus clustering. Subsequently, a prognostic risk model comprising 5 ICDGs was constructed using Lasso-Cox regression in the TCGA training cohort and further tested in the GEO cohort. Enriched pathways among the subtypes were analyzed using GO, KEGG, and GSVA. Furthermore, the immune microenvironment was assessed using ESTIMATE, CIBERSORT, and ssGSEA analyses. RESULTS: Consensus clustering divided LUAD patients into three ICDG subtypes with significant differences in prognosis and the immune microenvironment. A prognostic risk model was constructed based on 5 ICDGs and it was used to classify the patients into two risk groups; the high-risk group had poorer prognosis and an immunosuppressive microenvironment characterized by low immune score, low immune status, high abundance of immunosuppressive cells, and high expression of tumor purity. Cox regression, ROC curve analysis, and a nomogram indicated that the risk model was an independent prognostic factor. The five hub genes were verified by TCGA database, cell sublocalization immunofluorescence analysis, IHC images and qRT-PCR, which were consistent with bioinformatics analysis. CONCLUSIONS: The molecular subtypes and a risk model based on ICDGs proposed in our study are both promising prognostic classifications in LUAD, which may provide novel insights for developing accurate targeted cancer therapies.

Activation of AMPK in platelets promotes the production of offspring.

Platelets are terminally differentiated anucleated cells, but they still have cell-like functions and can even produce progeny platelets. However, the mechanism of platelet sprouting has not been elucidated so far. Here, we show that when platelet-rich plasma(PRP) was cultured at 37°C, platelets showed a spore phenomenon. The number of platelets increased when given a specific shear force. It is found that AMP-related signaling pathways, such as PKA and AMPK are activated in platelets in the spore state. Meanwhile, the mRNA expression levels of genes, such as CNN3, CAPZB, DBNL, KRT19, and ESPN related to PLS1 skeleton proteins also changed. Moreover, when we use the AMPK activator AICAR(AI) to treat washed platelets, cultured platelets can still appear spore phenomenon. We further demonstrate that washed platelets treated with Forskolin, an activator of PKA, not only platelet sprouting after culture but also the AMPK is activated. Taken together, these data demonstrate that AMPK plays a key role in the process of platelet budding and proliferation, suggesting a novel strategy to solve the problem of clinical platelet shortage.

What is new? In this study, we showed that when platelet-rich plasma(PRP) was cultured at 37°C, platelets showed spore phenomenon and increased.It was found that AMP-related signaling pathways, such as PKA and AMPK were activated in platelets in the spore state.In addition, we found that PKA acts as an upstream kinase of AMPK.In the process of platelet sprouting and proliferation, the mRNA expression levels of skeleton protein PLS1 and its related genes, such as CNN3, CAPZB, DBNL, KRT19, andESPN also changed.What is the impact? Our study proposes a new strategy to solve the problem of clinical platelet shortage.

Confinement of Sustainable Carbon Dots Results in Long Afterglow Emitters and Photocatalyst for Radical Photopolymerization.

Sustainable carbon dots based on cellulose, particularly carboxymethyl cellulose carbon dots (CMCCDs), were confined in an inorganic network resulting in CMCCDs@SiO2. This resulted in a material exhibiting long afterglow covering a time frame of several seconds also under air. Temperature-dependent emission spectra gave information on thermally activated delayed fluorescence (TADF) and room temperature phosphorescence (RTP) while photocurrent experiments provided a deeper understanding of charge availability in the dark period, and therefore, its availability on the photocatalyst surface. The photo-ATRP initiator, ethyl α-bromophenylacetate (EBPA), quenched the emission from the millisecond to the nanosecond time frame indicating participation of the triplet state in photoinduced electron transfer (PET). Both free radical and controlled radical polymerization based on photo-ATRP protocol worked successfully. Metal-free photo-ATRP resulted in chain extendable macroinitiators based on a reductive mechanism with either MMA or in combination with styrene. Addition of 9 ppm Cu2+ resulted in Mw/Mn of 1.4 while an increase to 72 ppm improved uniformity of the polymers; that is Mw/Mn=1.03. Complementary experiments with kerria laca carbon dots confined materials, namely KCDs@SiO2, provided similar results. Deposition of Cu2+ (9 ppm) on the photocatalyst surface explains better uniformity of the polymers formed in the ATRP protocol.

[Preliminary application of antibiotic bone cement directly inducing skin regeneration technology in repairing of wound in lateral toe flap donor area].

Objective: To investigate the feasibility and effectiveness of antibiotic bone cement directly inducing skin regeneration technology in the repairing of wound in the lateral toe flap donor area. Methods: Between June 2020 and February 2023, antibiotic bone cement directly inducing skin regeneration technology was used to repair lateral toe flap donor area in 10 patients with a total of 11 wounds, including 7 males and 3 females. The patients' age ranged from 21 to 63 years, with an average of 40.6 years. There were 3 cases of the distal segment of the thumb, 2 cases of the distal segment of the index finger, 1 case of the middle segment of the index and middle fingers, 1 case of the distal segment of the middle finger, and 3 cases of the distal segment of the ring finger. The size of the skin defect of the hand ranged from 2.4 cm×1.8 cm to 4.3 cm×3.4 cm. The disease duration ranged from 1 to 15 days, with an average of 6.9 days. The flap donor sites were located at fibular side of the great toe in 5 sites, tibial side of the second toe in 5 sites, and tibial side of the third toe in 1 site. The skin flap donor site wounds could not be directly sutured, with 2 cases having exposed tendons, all of which were covered with antibiotic bone cement. Results: All patients were followed up 6 months to 2 years, with an average of 14.7 months. All the 11 flaps survived and had good appearance. The wound healing time was 40-72 days, with an average of 51.7 days. There was no hypertrophic scar in the donor site, which was similar to the color of the surrounding normal skin; the appearance of the foot was good, and wearing shoes and walking of the donor foot were not affected. Conclusion: It is a feasible method to repair the wound in the lateral foot flap donor area with the antibiotic bone cement directly inducing skin regeneration technology. The wound heals spontaneously, the operation is simple, and there is no second donor site injury.

Use of Interfacial Interactions and Complexation of Carbon Dots to Construct Ultra-Robust and Efficient Photothermal Film From Micro-Carbonized Polysaccharides.

Solar energy conversion technologies, particularly solar-driven photothermal conversion, are both clean and manageable. Although much progress has been made in designing solar-driven photothermal materials, significant challenges remain, not least the photobleaching of organic dyes. To tackle these issues, micro-carbonized polysaccharide chains, with carbon dots (CDs) suspended from the chains, are conceived, just like grapes or tomatoes hanging from a vine. Carbonization of sodium carboxymethyl cellulose (CMC) produces just such a structure (termed CMC-g-CDs), which is used to produce an ultra-stable, robust, and efficient solar-thermal film by interfacial interactions within the CMC-g-CDs. The introduction of the CDs into the matrix of the photothermal material effectively avoided the problem of photobleaching. Manipulating the interfacial interactions (such as electrostatic interactions, van der Waals interactions, π-π stacking, and hydrogen bonding) between the CDs and the polymer chains markedly enhances the mechanical properties of the photothermal film. The CMC-g-CDs are complexed with Fe3+ to eliminate leakage of the photothermal reagent from the matrix and to solve the problem of poor water resistance. The resulting film (CMC-g-CDs-Fe) has excellent prospects for practical application as a photothermal film.

Rapid Rescue of Goose Astrovirus Genome via Red/ET Assembly.

The host-specific infection of Avian Astrovirus (AAstVs) has posed significant challenges to the poultry industry, resulting in substantial economic losses. However, few reports exist on the functional consequences of genome diversity, cross-species infectivity and mechanisms governing virus replication of AAstVs, making it difficult to develop measures to control astrovirus transmission. Reverse genetics technique can be used to study the function of viruses at the molecular level, as well as investigating pathogenic mechanisms and guide vaccine development and disease treatment. Herein, the reverse genetics technique of goose astrovirus GAstV/JS2019 strain was developed based on use of a reconstructed vector including CMV promotor, hammerhead ribozyme (HamRz), hepatitis delta virus ribozyme (HdvRz), and SV40 tail, then the cloned viral genome fragments were connected using Red/ET recombineering. The recombinant rGAstV-JS2019 was readily rescued by transfected the infectious clone plasmid into LMH cells. Importantly, the rescued rGAstV/JS2019 exhibited similar growth kinetics comparable to those of the parental GAstV/JS2019 isolate in cultured cells. Our research results provide an alternative and more effective reverse genetic tool for a detailed understanding of viral replication, pathogenic mechanisms, and molecular mechanisms of evolution.

Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration.

BACKGROUND: Evidence from observational studies suggests an association between chronic obstructive pulmonary disease (COPD) and lung cancer. The potential interactions between the immune system and the lungs may play a causative role in COPD and lung cancer and offer therapeutic prospects. However, the causal association and the immune-mediated mechanisms between COPD and lung cancer remain to be determined. METHODS: We employed a two-sample Mendelian randomization (MR) approach to investigate the causal association between COPD and lung cancer. Additionally, we examined whether immune cell signals were causally related to lung cancer, as well as whether COPD was causally associated with immune cell signals. Furthermore, through two-step Mendelian randomization, we investigated the mediating effects of immune cell signals in the causal association between COPD and lung cancer. Leveraging publicly available genetic data, our analysis included 468,475 individuals of European ancestry with COPD, 492,803 individuals of European ancestry with lung cancer, and 731 immune cell signatures of European ancestry. Additionally, we conducted single-cell transcriptome sequencing analysis on COPD, lung cancer, and control samples to validate our findings. FINDINGS: We found a causal association between COPD and lung cancer (odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.31-2.02, P-value < 0.001). We also observed a causal association between COPD and regulatory T cells (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.01-1.40, P-value < 0.05), as well as a causal association between regulatory T cells and lung cancer (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 1.002-1.045, P-value < 0.05). Furthermore, our two-step Mendelian randomization analysis demonstrated that COPD is associated with lung cancer through the mediation of regulatory T cells. These findings were further validated through single-cell sequencing analysis, confirming the mediating role of regulatory T cells in the association between COPD and lung cancer. INTERPRETATION: As far as we are aware, we are the first to combine single-celled immune cell data with two-sample Mendelian randomization. Our analysis indicates a causal association between COPD and lung cancer, with regulatory T cells playing an intermediary role.

Comprehensive single-cell transcriptomic profiling reveals molecular subtypes and prognostic biomarkers with implications for targeted therapy in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a genetically heterogeneous disease with poor clinical outcomes. Identification of biomarkers linked to DNA replication stress may enable improved prognostic risk stratification and guide therapeutic decision making. We performed integrated single-cell RNA sequencing and computational analyses to define the molecular determinants and subtypes underlying ESCC heterogeneity. METHODS: Single-cell RNA sequencing was performed on ESCC samples and analyzed using Seurat. Differential gene expression analysis was used to identify esophageal cell phenotypes. DNA replication stress-related genes were intersected with single-cell differential expression data to identify potential prognostic genes, which were used to generate a DNA replication stress (DRS) score. This score and associated genes were evaluated in survival analysis. Putative prognostic biomarkers were evaluated by Cox regression and consensus clustering. Mendelian randomization analyses assessed the causal role of PRKCB. RESULTS: High DRS score associated with poor survival. Four genes (CDKN2A, NUP155, PPP2R2A, PRKCB) displayed prognostic utility. Three molecular subtypes were identified with discrete survival and immune properties. A 12-gene signature displayed robust prognostic performance. PRKCB was overexpressed in ESCC, while PRKCB knockdown reduced ESCC cell migration. CONCLUSIONS: This integrated single-cell sequencing analysis provides new insights into the molecular heterogeneity and prognostic determinants underlying ESCC. The findings identify potential prognostic biomarkers and a gene expression signature that may enable improved patient risk stratification in ESCC. Experimental validation of the role of PRKCB substantiates the potential clinical utility of our results.

Illuminating Shared Genetic Associations Between Oesophageal Carcinoma and Pulmonary Carcinoma Risk.

Background: Lung cancer and oesophageal cancer are prevalent malignancies with rising incidence and mortality worldwide. While some environmental and behavioural risk factors for these cancers are established, the contribution of genetic factors to their pathogenesis remains incompletely defined. This study aimed to interrogate the intricate genetic relationship between lung cancer and oesophageal cancer and their potential comorbidity. Methods: We utilised linkage disequilibrium score regression (LDSC) to analyse the genetic correlation between oesophageal carcinoma and lung carcinoma. We then employed several approaches, including pleiotropic analysis under the composite null hypothesis (PLACO), multi-marker analysis of genomic annotation (MAGMA), cis-expression quantitative trait loci (eQTL) analysis, and a pan-cancer assessment to identify pleiotropic loci and genes. Finally, we performed bidirectional Mendelian randomisation (MR) to evaluate the causal relationship between these malignancies. Results: LDSC revealed a significant genetic correlation between oesophageal carcinoma and lung carcinoma. Further analysis identified shared gene loci including PGBD1, ZNF323, and WNK1 using PLACO. MAGMA identified enriched pathways and 9 pleiotropic genes including HIST1H1B, HIST1H4L, and HIST1H2BL. eQTL analysis integrating oesophageal, lung, and blood tissues revealed 26 shared genes including TERT, NKAPL, RAD52, BTN3A2, GABBR1, CLPTM1L, and TRIM27. A pan-cancer exploration of the identified genes was undertaken. MR analysis showed no evidence for a bidirectional causal relationship between oesophageal carcinoma and lung carcinoma. Conclusions: This study provides salient insights into the intricate genetic links between lung carcinoma and oesophageal carcinoma. Utilising multiple approaches for genetic correlation, locus and gene analysis, and causal assessment, we identify shared genetic susceptibilities and regulatory mechanisms. These findings reveal new leads and targets to further elucidate the genetic basis of lung and oesophageal carcinoma, aiding development of preventive and therapeutic strategies.

Biobased and biodegradable films exhibiting circularly polarized room temperature phosphorescence.

There is interest in developing sustainable materials displaying circularly polarized room-temperature phosphorescence, which have been scarcely reported. Here, we introduce biobased thin films exhibiting circularly polarized luminescence with simultaneous room-temperature phosphorescence. For this purpose, phosphorescence-active lignosulfonate biomolecules are co-assembled with cellulose nanocrystals in a chiral construct. The lignosulfonate is shown to capture the chirality generated by cellulose nanocrystals within the films, emitting circularly polarized phosphorescence with a 0.21 dissymmetry factor and 103 ms phosphorescence lifetime. By contrast with most organic phosphorescence materials, this chiral-phosphorescent system possesses phosphorescence stability, with no significant recession under extreme chemical environments. Meanwhile, the luminescent films resist water and humid environments but are fully biodegradable (16 days) in soil conditions. The introduced bio-based, environmentally-friendly circularly polarized phosphorescence system is expected to open many opportunities, as demonstrated here for information processing and anti-counterfeiting.

A Risk Score Based on Immune- and Oxidative Stress-Related LncRNAs Predicts Prognosis in Lung Adenocarcinoma: Insights from in vitro Experiments and Large-Scale Transcriptome Analysis.

Background: Long non-coding RNAs (lncRNAs) were demonstrated to be key to cancer progression and highly associated with the tumor immune microenvironment. Oxidative stress and immune may modulate the biological behaviors of tumors. Therefore, biomarkers that combined oxidative stress, immune, and lncRNA can be a promising candidate bioindicator in clinical therapy of cancers. Methods: Immune-related genes (IRGs) and oxidative stress-related genes (ORGs) were identified based on a detailed review of published literatures. The transcriptome data and clinical information of lung adenocarcinoma (LUAD) patients were obtained from TCGA database. Lasso and Cox regression analyses were conducted to develop a prognostic model. Additionally, the link between immune checkpoints, immune cells, and the prognostic model was investigated, and predict the sensitivity of immunotherapy. Results: 2498 IRGs and 809 ORGs were extracted from previous studies, and 190 immune- and oxidative stress-related genes (IOGs) were acquired by overlapping the above genes. 658 immune- and oxidative stress-related lncRNAs (IOLs) were screened by Pearson correlation analysis. A total of 25 prognosis-related IOLs were screened by univariate regression analysis. Finally, LASSO Cox regression analysis was adopted for determining a 12-IOLs prognostic risk signature. The signature performance was confirmed in the training cohort and the testing cohort, and cases were classified into low- and high-risk groups by the risk score calculated from the signature. Patients in the high-risk group had poor prognoses and immunosuppression, while the risk score was significantly associated with tumor-infiltrating immune cells, immune checkpoint expression, and immunotherapy responses. In vitro experiments further confirmed the expression of key signature gene. Conclusion: Our new IOLs-related prognostic signature can be reliable prognostic tools and therapeutic targets for LUAD patients.