RBM22 regulates RNA polymerase II 5' pausing, elongation rate, and termination by coordinating 7SK-P-TEFb complex and SPT5.

BACKGROUND: Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular mechanisms of their involvement in transcriptional processes remain poorly understood. RESULTS: Here, we describe a direct role of splicing factor RBM22 in coordinating multiple steps of RNA Polymerase II (RNAPII) transcription in human cells. The RBM22 protein widely occupies the RNAPII-transcribed gene locus in the nucleus. Loss of RBM22 promotes RNAPII pause release, reduces elongation velocity, and provokes transcriptional readthrough genome-wide, coupled with production of transcripts containing sequences from downstream of the gene. RBM22 preferentially binds to the hyperphosphorylated, transcriptionally engaged RNAPII and coordinates its dynamics by regulating the homeostasis of the 7SK-P-TEFb complex and the association between RNAPII and SPT5 at the chromatin level. CONCLUSIONS: Our results uncover the multifaceted role of RBM22 in orchestrating the transcriptional program of RNAPII and provide evidence implicating a splicing factor in both RNAPII elongation kinetics and termination control.

Leukocyte counts and ratios as potential predictors of large vessel occlusion in acute ischemic stroke: A retrospective cohort study.

Leukocyte counts and ratios are independent biomarkers to determine the severity and prognosis of acute ischemic stroke (AIS). In AIS, the connection between leukocytes and large vessel occlusion (LVO) is uncertain. This study aims to determine the relationship between the existence of LVO and leukocyte counts and ratios on admission to AIS. Patients were retrospectively evaluated within six hours of AIS starting between January 2019 and April 2023. On admission, blood specimens were collected, and leukocyte subtype counts were promptly analyzed. Computed tomography or digital subtraction angiography were utilized to verify the existence of LVO. Regression analysis and receiver operating characteristic (ROC) curves were employed to investigate the connections between the counts and ratios of leukocytes and the existence of LVO, as well as the discriminatory ability of these variables in predicting LVO. Total white blood cell (WBC) count, neutrophil count, and neutrophil-to-lymphocyte ratio (NLR) were substantially higher in the LVO existence group compared to the LVO absence group, whereas the ratio of eosinophils to neutrophils (ENR × 102) was lower (P < .001, respectively). Significant associations were observed between total WBC counts, neutrophil counts, NLR, and ENR × 102 and the existence of LVO (P < .001, respectively). Total WBC counts, neutrophil counts, NLR, and ENR × 102 had respective areas under the curves (AUC) of 0.730, 0.748, 0.704, and 0.680 for identifying LVO. Our results show that in AIS patients, the existence of LVO is independently associated with elevated total WBC and neutrophil counts, high NLR, and low ENR × 102 levels. Neutrophil and total WBC counts, as well as NLR and levels of ENR × 102, may serve as potential biomarkers for predicting LVO. Neuroinflammation, based on the existence of LVO, should be given particular attention in future investigations.

A Lignin Silver Nanoparticles/Polyvinyl Alcohol/Sodium Alginate Hybrid Hydrogel with Potent Mechanical Properties and Antibacterial Activity.

Antibacterial hydrogels have attracted significant attention due to their diverse applications, efficient antimicrobial properties, and adaptability to various environments and requirements. However, their relatively fragile structure, coupled with the potential for environmental toxicity when exposed to their surroundings for extended periods, may significantly limit their practical application potential. In this work, a composite hydrogel was synthesized with outstanding mechanical features and antibacterial capability. The hydrogel was developed through the combination of the eco-friendly and enduring antibacterial agent, lignin silver nanoparticles (Lig-Ag NPs), with polyvinyl alcohol (PVA) and sodium alginate (SA), in varying proportions. The successful synthesis of the hydrogel and the dispersed distribution of Lig-Ag NPs within the hydrogel were confirmed by various analytical techniques, including field emission scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), mercury intrusion porosimetry (MIP), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The formation of multiple hydrogen bonds between Lig-Ag NPs and the composites contributed to a more stable and dense network structure of the hydrogel, consequently enhancing its mechanical properties. Rheological tests revealed that the hydrogel exhibited an elastic response and demonstrated outstanding self-recovery properties. Significantly, the antibacterial hydrogel demonstrated effectiveness against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), achieving a <5% survival of bacteria within 12 h. This study presented a green and straightforward synthetic strategy for the application of antibacterial composite hydrogels in various fields.

Single-cell analysis reveals insights into epithelial abnormalities in ovarian endometriosis.

Ovarian endometriosis is characterized by the growth of endometrial tissue within the ovary, causing infertility and chronic pain. However, its pathophysiology remains unclear. Utilizing high-precision single-cell RNA sequencing, we profile the normal, eutopic, and ectopic endometrium from 34 individuals across proliferative and secretory phases. We observe an increased proportion of ciliated cells in both eutopic and ectopic endometrium, characterized by a diminished expression of estrogen sulfotransferase, which likely confers apoptosis resistance. After translocating to ectopic lesions, endometrial epithelium upregulates nicotinamide N-methyltransferase expression that inhibits apoptosis by promoting deacetylation and subsequent nuclear exclusion of transcription factor forkhead box protein O1, thereby leading to the downregulation of the apoptotic gene BIM. Moreover, epithelial cells in ectopic lesions elevate HLA class II complex expression, which stimulates CD4+ T cells and consequently contributes to chronic inflammation. Altogether, our study provides a comprehensive atlas of ovarian endometriosis and highlights potential therapeutic targets for modulating apoptosis and inflammation.

Ebselen and TPI-1, as RecG helicase inhibitors, potently enhance the susceptibility of Pseudomonas aeruginosa to DNA damage agents.

Holliday junction (HJ) is a four-way structured DNA intermediate in processes of homologous recombination and DNA double-stranded break (DSB) repair. In bacteria, HJs are processed via either the RuvABC or RecG-dependent pathways. In addition, RecG also plays a critical role in the reactivation of stalled replication forks, making it an attractive target for antibacterial drug development. Here, we conducted a high-throughput screening targeting the RecG helicase from a common opportunistic pathogen Pseudomonas aeruginosa (Pa). From a library containing 7920 compounds, we identified Ebselen and TPI-1 (2',5'-Dichloro-[1,1'-biphenyl]-2,5-dione) as two potent PaRecG inhibitors, with IC50 values of 0.31 ± 0.02 µM and 1.16 ± 0.06 µM, respectively. Further biochemical analyses suggested that both Ebselen and TPI-1 inhibited the ATPase activity of PaRecG, and hindered its binding to HJ DNA with high selectivity. These compounds, when combined with our previously reported RuvAB inhibitors, resulted in more severe DNA repair defects than the individual treatment, and potently enhanced the susceptibility of P. aeruginosa to the DNA damage agents. This work reports novel small molecule inhibitors of RecG, offering valuable chemical tools for advancing our understanding of RecG's function and mechanism. Additionally, these inhibitors might be further developed as promising antibacterial agents in the fight against P. aeruginosa infections.

A Unified Spatio-Temporal Inference Network for Car-Sharing Serial Prediction.

Car-sharing systems require accurate demand prediction to ensure efficient resource allocation and scheduling decisions. However, developing precise predictive models for vehicle demand remains a challenging problem due to the complex spatio-temporal relationships. This paper introduces USTIN, the Unified Spatio-Temporal Inference Prediction Network, a novel neural network architecture for demand prediction. The model consists of three key components: a temporal feature unit, a spatial feature unit, and a spatio-temporal feature unit. The temporal unit utilizes historical demand data and comprises four layers, each corresponding to a different time scale (hourly, daily, weekly, and monthly). Meanwhile, the spatial unit incorporates contextual points of interest data to capture geographic demand factors around parking stations. Additionally, the spatio-temporal unit incorporates weather data to model the meteorological impacts across locations and time. We conducted extensive experiments on real-world car-sharing data. The proposed USTIN model demonstrated its ability to effectively learn intricate temporal, spatial, and spatiotemporal relationships, and outperformed existing state-of-the-art approaches. Moreover, we employed negative binomial regression with uncertainty to identify the most influential factors affecting car usage.

Custom-designed polyphenol lignin for the enhancement of poly(vinyl alcohol)-based wood adhesive.

Adhesives are used extensively in the wood industry. As resource and environmental issues become increasingly severe, the development of green and sustainable biomass-based adhesives has attracted increasing attention. In this work, a green wood adhesive is developed from poly(vinyl alcohol) and lignin with molecular designs of lignin extending beyond those in nature. The lignin undergoes extraction from corncob residue, aldehydration, and phenolisation (phenol, resorcinol, and catechol) to significantly increase the phenolic hydroxyl groups (over 7.92 mmol/g), which has the effect of enhancing the hydrogen bonding force between the adhesive and the wood, thereby greatly improving adhesive performance. Compared with pure PVA, polyphenol lignin-containing PVA showed improved adhesion strength and hydrophobicity. PVA/resorcinol-lignin has the significantly improved wood lap shear strength (6.27 MPa, 77.6 % improvement) and hydrophobicity (almost 100 % increase in wet shear strength). This research not only provides a green and high-performance alternative raw material for wood adhesives but also broadens the path for large-scale application of biomass.

Ubiquitination, SUMOylation, and NEDDylation related genes serve as prognostic and therapeutic biomarkers for oral squamous cell carcinoma.

BACKGROUND: Ubiquitination, small ubiquitin-related modifiers, and NEDDylation are now found to function in cancer biology; however, its role in the oral cancer patients remains unclear. METHODS: A set of bioinformatic tools was integrated to analyze the expression and prognostic significance of ubiquitin and ubiquitin-like (UB/UBL) genes. A UB/UBL-related risk score was developed via correlation analyses, univariate Cox regression, and multivariate Cox regression. Nomogram analysis evaluates the model's prediction performance. The drug sensitivity analysis, immune profiles of UB/UBL-classified oral squamous cell carcinoma (OSCC) patients, and their related function pathway were investigated, and the role of UB/UBL-related genes in drug therapy was analyzed. RESULTS: A total of six prognostic UB/UBL-related genes were obtained. PSMD3, PCGF2, and H2BC10 were significantly downregulated in OSCC tissue and associated with longer survival time. OSCC patients in the high-risk group showed a significantly lower overall survival and enriched in cancer-related pathways. The prognostic potential of genes associated with UB/UBL was discovered, and patients with high-risk scores showed an increase of protumor immune infiltrates and a high expression of immune checkpoints. Moreover, the area under the curve of the annual survival rate was 0.616, 0.671, and 0.673, respectively. Besides, patients in the high-risk group are more sensitive to docetaxel, doxorubicin, and methotrexate therapy. CONCLUSIONS: We construct a prognosis model for OSCC patients with UB/UBL-related genes and try to find a new approach to treating oral cancer patients. The UB/UBL-related signature is helpful in developing new tumor markers, prognostic prediction, and in guiding treatment for OSCC patients.

Efficacy of personalized 3D-printed osteotomy guide in maximizing fibular utilization and minimizing graft length for reconstruction of large mandibular defect.

OBJECTIVE: The study addresses the long-standing challenge of insufficient length in vascularized fibular flaps when reconstructing large mandibular defects that require dual-barrel grafts. Employing personalized 3D-printed osteotomy guides, the study aims to optimize fibular utilization and minimize the required graft length. MATERIAL AND METHODS: Two reconstruction methods for distal bone defects were compared: a fold-down (FD) group that employed a specialized osteotomy guide for folding down a triangular bone segment, and a traditional double-barrel (DB) group. Metrics for comparison included defect and graft lengths, as well as the graft-to-defect length ratio. Postoperative quality of life was assessed using the University of Washington Quality of Life questionnaire (UW-QoL). RESULT: Both FD and DB groups achieved successful mandibular reconstruction. Despite larger defects in the FD group (117 ± 31.35 mm vs 84 ± 35.34 mm, p = 0.028), the used fibula length was not statistically longer in the FD group. The median ratio of graft-to-defect length was also lower in the FD group (1.327 vs 1.629, p = 0.024), suggesting that FD required only 82.47% of the graft length needed in the DB approach. Quality of life scores post-surgery were comparable between the groups. CONCLUSION: Personalized 3D-printed osteotomy guides enhance fibula graft efficacy for reconstructing larger mandibular defects, necessitating shorter graft lengths while preserving postoperative quality of life. CLINICAL RELEVANCE: This study confirms the utility of 3D printing technology as an effective and precise tool in orthopedic surgery, particularly for complex reconstructions like large mandibular defects. It suggests a viable alternative that could potentially revolutionize current practices in bone grafting.

Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway.

OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION: FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

Bioinspired multiscale cellulose/lignin-silver composite films with robust mechanical, antioxidant and antibacterial properties for ultraviolet shielding.

Constructing a high-performance ultraviolet shielding film is an effective way for addressing the growing problem of ultraviolet radiation. However, it is still a great challenge to achieve a combination of multifunctional, excellent mechanical properties and low cost. Here, inspired by the multiscale structure of biomaterials and features of lignin, a multifunctional composite film (CNF/CMF/Lig-Ag) is constructed via a facile vacuum-filtration method by introducing micron-sized cellulose fibers (CMF) and lignin-silver nanoparticles (Lig-Ag NPs) into the cellulose nanofibers (CNF) film network. In this composite film, the microfibers interweave with nanofibers to form a multiscale three-dimensional network, which ensures satisfactory mechanical properties of the composite film. Meanwhile, the Lig-Ag NPs are employed as a multifunctional filler to enhance the composite film's antioxidant, antibacterial and ultraviolet shielding abilities. As a result, the prepared CNF/CMF/Lig-Ag composite film demonstrates excellent mechanical properties (with tensile strength of 133.8 MPa and fracture strain of 7.4 %), good biocompatibility, high thermal stability, potent antioxidant and antibacterial properties. More importantly, such composite film achieves a high ultraviolet shielding rate of 98.2 % for ultraviolet radiation A (UVA) and 99.4 % for ultraviolet radiation B (UVB), respectively. Therefore, the prepared CNF/CMF/Lig-Ag composite film shows great potential in application of ultraviolet protection.

Based on metabolomics, the optimum wind speed process parameters of flue-cured tobacco in heat pump bulk curing barn were explored.

To explore the influence of wind speed on the quality of tobacco in this study, we employed a heat pump-powered intensive curing barn and a three-stage curing process. By evaluating the influence of fan parameters on the quality of tobacco leaves at different curing stages, the optimal wind speed was determined. After adopting the optimized wind speed process, the degradation of macromolecular substances was faster, the accumulation of aroma substances was delayed to 55 °C, and the accumulation was more complete. Among them, the contents of reducing sugar and total sugar in flue-cured tobacco leaves were 22.25% and 29.2%, respectively, which were lower than those in the control group. The sugar was converted into more aroma substances, and the total amount of neutral aroma substances was 48.82% higher than that of the control group. The content of related aroma substances increased significantly. The content of petroleum ether extract related to aroma substances increased by 0.93% compared with the control group. The macromolecular substances were degraded more fully than the control group, such as the starch content decreased to 1.56%. The results of metabolomics showed that the contents of aldehydes, heterocyclic compounds, alcohols, ketones and esters increased significantly in different degrees after this process. These results show that the optimization of wind speed parameters can significantly improve the baking quality of tobacco leaves. This study provides a reference for the optimization of the flue-cured tobacco baking process.

ABO-incompatible living donor kidney transplantation failure due to acute blood group antibody-dependent rejection triggered by human parvovirus B19 infection: a case report and literature review.

Background: With the improvement of immunosuppressive regimens, the success rate and availability of ABO-incompatible (ABO-i) kidney transplantation (KT) have gradually increased. However, the management of immunosuppression protocols and complications associated with ABO-i KT is complex. Here, we report a clinical case of ABO-i living donor KT with allograft dysfunction caused by acute blood group antibody-dependent rejection triggered by human parvovirus B19 (B19V). Case report: The ABO blood group of the recipient was O, and that of the donor was B. The recipient had high baseline anti-B antibody titers (IgM, 1:1024; IgG, 1:64). Before transplantation, he completed a desensitization protocol comprising plasma exchange, double-filtration plasmapheresis, and rituximab, which maintained a low blood group antibody level and resulted in successful transplantation. Two weeks after surgery, the recipient developed a B19V infection combined with acute T-cell-mediated rejection. After the anti-rejection regimen, acute rejection (AR) was successfully reversed, but B19V persisted. One week after AR stabilization, the patient experienced acute antibody-mediated rejection that was more severe and refractory, resulting in the loss of the transplanted kidney. Conclusion: Desensitization combined with immunosuppressants can lead to overimmunosuppression and cause various infections. Infections could break the accommodation state of the patient, thereby inducing AR and resulting in the loss of the transplanted kidney.

Atomically accurate site-specific ligand tailoring of highly acid- and alkali-resistant Ti(iv)-based metallamacrocycle for enhanced CO2 photoreduction.

Skillfully engineering surface ligands at specific sites within robust clusters presents both a formidable challenge and a captivating opportunity. Herein we unveil an unprecedented titanium-oxo cluster: a calix[8]arene-stabilized metallamacrocycle (Ti16L4), uniquely crafted through the fusion of four "core-shell" {Ti4@(TBC[8])(L)} subunits with four oxalate moieties. Notably, this cluster showcases an exceptional level of chemical stability, retaining its crystalline integrity even when immersed in highly concentrated acid (1 M HNO3) and alkali (20 M NaOH). The macrocycle's surface unveils four specific, customizable µ2-bridging sites, primed to accommodate diverse carboxylate ligands. This adaptability is highlighted through deliberate modifications achieved by alternating crystal soaking in alkali and carboxylic acid solutions. Furthermore, Ti16L4 macrocycles autonomously self-assemble into one-dimensional nanotubes, which subsequently organize into three distinct solid phases, contingent upon the specific nature of the four µ2-bridging ligands. Notably, the Ti16L4 exhibit a remarkable capacity for photocatalytic activity in selectively reducing CO2 to CO. Exploiting the macrocycle's modifiable shell yields a significant boost in performance, achieving an exceptional maximum CO release rate of 4.047 ± 0.243 mmol g-1 h-1. This study serves as a striking testament to the latent potential of precision-guided surface ligand manipulation within robust clusters, while also underpinning a platform for producing microporous materials endowed with a myriad of surface functionalities.

Sirolimus in combination with low-dose extended-release tacrolimus in kidney transplant recipients.

Introduction: Many challenges remain for long-term survival of renal allografts. Once-daily sirolimus (SRL) combined with low-dose extended-release tacrolimus (LER-TAC) may improve medication adherence and reduce the potential nephrotoxicity of calcineurin inhibitors (CNI) compared with standard immunosuppression regimens, thus potentially improving long-term graft survival. Methods: This retrospective, observational, single-center, propensity score matching (PSM) study compared conversion to SRL combined with low-dose ER-TAC and mycophenolic acid (MPA) combined with standard-dose TAC in kidney transplant recipients. After PSM, there were 56 patients in each group. Efficacy, safety, and medication adherence were evaluated over 12 months. Results: There was no significant difference between the two groups in terms of graft and recipient survival and incidence of biopsy-proven acute rejection (p = 1.000), and none of the recipients developed dnDSA after conversion. The mean eGFR improved in SRL + LER-TAC group after conversion compared to before conversion (51.12 ± 20.1 ml/min/1.73 m2 vs. 56.97 ± 19.23 ml/min/1.73 m2, p < 0.05). The medication adherence at 12 months after conversion was superior to before conversion (p = 0.002). Discussion: Our findings suggest that an immunosuppressive regimen of SRL combined with low-dose ER-TAC is no less effective and safe than standard immunosuppressive regimens for renal transplant recipients and may improve graft renal function and medication adherence.

Heterologous Naringenin Production in the Filamentous Fungus Penicillium rubens.

Naringenin is a natural product with several reported bioactivities and is the key intermediate for the entire class of plant flavonoids. The translation of flavonoids into modern medicine as pure compounds is often hampered by their low abundance in nature and their difficult chemical synthesis. Here, we investigated the possibility to use the filamentous fungus Penicillium rubens as a host for flavonoid production. P. rubens is a well-characterized, highly engineered, traditional "workhorse" for the production of ß-lactam antibiotics. We integrated two plant genes encoding enzymes in the naringenin biosynthesis pathway into the genome of the secondary metabolite-deficient P. rubens 4xKO strain. After optimization of the fermentation conditions, we obtained an excellent molar yield of naringenin from fed p-coumaric acid (88%) with a titer of 0.88 mM. Along with product accumulation over 36 h, however, we also observed rapid degradation of naringenin. Based on high-resolution mass spectrometry analysis, we propose a naringenin degradation pathway in P. rubens 4xKO, which is distinct from other flavonoid-converting pathways reported in fungi. Our work demonstrates that P. rubens is a promising host for recombinant flavonoid production, and it represents an interesting starting point for further investigation into the utilization of plant biomass by filamentous fungi.

Novel Information-Driven Smoothing Spline Linearization Method for High-Precision Displacement Sensors Based on Information Criterions.

A noise-resistant linearization model that reveals the true nonlinearity of the sensor is essential for retrieving accurate physical displacement from the signals captured by sensing electronics. In this paper, we propose a novel information-driven smoothing spline linearization method, which innovatively integrates one new and three standard information criterions into a smoothing spline for the high-precision displacement sensors' linearization. Using theoretical analysis and Monte Carlo simulation, the proposed linearization method is demonstrated to outperform traditional polynomial and spline linearization methods for high-precision displacement sensors with a low noise to range ratio in the 10-5 level. Validation experiments were carried out on two different types of displacement sensors to benchmark the performance of the proposed method compared to the polynomial models and the the non-smoothing cubic spline. The results show that the proposed method with the new modified Akaike Information Criterion stands out compared to the other linearization methods and can improve the residual nonlinearity by over 50% compared to the standard polynomial model. After being linearized via the proposed method, the residual nonlinearities reach as low as ±0.0311% F.S. (Full Scale of Range), for the 1.5 mm range chromatic confocal displacement sensor, and ±0.0047% F.S., for the 100 mm range laser triangulation displacement sensor.

A novel hypoxia-associated gene signature for prognosis prediction in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of head and neck, which seriously threatens human life and health. However, the mechanism of hypoxia-associated genes (HAGs) in HNSCC remains unelucidated. This study aims to establish a hypoxia-associated gene signature and the nomogram for predicting the prognosis of patients with HNSCC. METHODS: Previous literature reports provided a list of HAGs. The TCGA database provided genetic and clinical information on HNSCC patients. First, a hypoxia-associated gene risk model was constructed for predicting overall survival (OS) in HNSCC patients and externally validated in four GEO datasets (GSE27020, GSE41613, GSE42743, and GSE117973). Then, immune status and metabolic pathways were analyzed. A nomogram was constructed and assessed the predictive value. Finally, experimental validation of the core genes was performed by qRT-PCR. RESULTS: A HNSCC prognostic model was constructed based on 8 HAGs. This risk model was validated in four external datasets and exhibited high predictive value in various clinical subgroups. Significant differences in immune cell infiltration levels and metabolic pathways were found between high and low risk subgroups. The nomogram was highly accurate for predicting OS in HNSCC patients. CONCLUSIONS: The 8 hypoxia-associated gene signature can serve as novel independent prognostic indicators in HNSCC patients. The nomogram combining the risk score and clinical stage enhanced predictive performance in predicting OS compared to the risk model and clinical characteristics alone.

Heteroatom-engineered multicolor lignin carbon dots enabling bimodal fluorescent off-on detection of metal-ions and glutathione.

Carbon dots (CDs) have emerged as a promising subclass of optical nanomaterials with versatile functions in multimodal biosensing. Howbeit the rapid, reliable and reproducible fabrication of multicolor CDs from renewable lignin with unique groups (e.g., -OCH3, -OH and -COOH) and alterable moieties (e.g., ß-O-4, phenylpropanoid structure) remains challenging due to difficult-to-control molecular behavior. Herein we proposed a scalable acid-reagent strategy to engineer a family of heteroatom-doped multicolor lignin carbon dots (LCDs) that are functioned as the bimodal fluorescent off-on sensing of metal-ions and glutathione (GSH). Benefiting from the modifiable photophysical structure via heteroatom-doping (N, S, W, P and B), the multicolor LCDs (blue, green and yellow) with a controllable size distribution of 2.06-2.22 nm deliver the sensing competences to fluorometric probing the distinctive metal-ion systems (Fe3+, Al3+ and Cu2+) under a broad response interval (0-500 µM) with excellent sensitivity and limit of detection (LOD, 0.45-3.90 µM). Meanwhile, we found that the addition of GSH can efficiently restore the fluorescence of LCDs by forming a stable Fe3+-GSH complex with a LOD of 0.97 µM. This work not only sheds light on evolving lignin macromolecular interactions with tunable luminescent properties, but also provides a facile approach to synthesize multicolor CDs with advanced functionalities.