Impact of Postoperative Radiotherapy on the Prognosis of Early-Stage (pT1-2N0M0) Oral Tongue Squamous Cell Carcinoma.

PURPOSE: To identify subgroups of patients with early-stage (pT1-2N0M0) oral tongue squamous cell carcinoma (OTSCC) who may benefit from postoperative radiotherapy (PORT). PATIENTS AND METHODS: This retrospective cohort study included 528 patients diagnosed between October 2009 and December 2021. Clinicopathological characteristics and treatments with or without PORT were analyzed for their impact on outcomes. RESULTS: Among 528 patients who underwent radical surgery (median age, 62 years [IQR, 52-69]), 145 (27.5%) also underwent PORT. Multivariate analyses revealed that PORT was associated with improved survival outcomes, whereas moderate-to-poor differentiation, perineural infiltration (PNI), lymphovascular invasion (LVI), and increasing depth of invasion (DOI) were associated with poorer survival outcomes. For patients with moderate-to-poor differentiation, the surgery + PORT group showed improved outcomes compared with the surgery-alone group. After propensity score matching, the results were as follows: overall survival (OS), 97% versus 69%, P = .003; disease-free survival (DFS), 88% versus 50%, P = .001. After excluding cases with PNI/LVI, the differences persisted: OS, 97% versus 82%, P = .040; DFS, 87% versus 64%, P = .012. Similar survival benefits were observed in 104 patients with PNI and/or LVI (OS, 81% v 58%; P = .022; DFS, 76% v 47%; P = .002). In subgroups with DOI >5 mm or close margins, PORT contributed to improved DFS (80% v 64%; P = .006; 92% v 66%; P = .049) but did not significantly affect OS. CONCLUSION: Patients with moderately-to-poorly differentiated pT1-2N0M0 OTSCC benefited from PORT. Our study provided evidence that patients with PNI and/or LVI who underwent PORT had improved survival. PORT also offered DFS benefit among patients with DOI >5 mm.

Novel Pyrazole-4-Carboxamide Derivatives Containing Oxime Ether Group as Potential SDHIs to Control Rhizoctonia solani.

In the search for novel succinate dehydrogenase inhibitor (SDHI) fungicides to control Rhizoctonia solani, thirty-five novel pyrazole-4-carboxamides bearing either an oxime ether or an oxime ester group were designed and prepared based on the strategy of molecular hybridization, and their antifungal activities against five plant pathogenic fungi were also investigated. The results indicated that the majority of the compounds containing oxime ether demonstrated outstanding in vitro antifungal activity against R. solani, and some compounds also displayed pronounced antifungal activities against Sclerotinia sclerotiorum and Botrytis cinerea. Particularly, compound 5e exhibited the most promising antifungal activity against R. solani with an EC50 value of 0.039 µg/mL, which was about 20-fold better than that of boscalid (EC50 = 0.799 µg/mL) and 4-fold more potent than fluxapyroxad (EC50 = 0.131 µg/mL). Moreover, the results of the detached leaf assay showed that compound 5e could suppress the growth of R. solani in rice leaves with significant protective efficacies (86.8%) at 100 µg/mL, superior to boscalid (68.1%) and fluxapyroxad (80.6%), indicating promising application prospects. In addition, the succinate dehydrogenase (SDH) enzymatic inhibition assay revealed that compound 5e generated remarkable SDH inhibition (IC50 = 2.04 µM), which was obviously more potent than those of boscalid (IC50 = 7.92 µM) and fluxapyroxad (IC50 = 6.15 µM). Furthermore, SEM analysis showed that compound 5e caused a remarkable disruption to the characteristic structure and morphology of R. solani hyphae, resulting in significant damage. The molecular docking analysis demonstrated that compound 5e could fit into the identical binding pocket of SDH through hydrogen bond interactions as well as fluxapyroxad, indicating that they had a similar antifungal mechanism. The density functional theory and electrostatic potential calculations provided useful information regarding electron distribution and electron transfer, which contributed to understanding the structural features and antifungal mechanism of the lead compound. These findings suggested that compound 5e could be a promising candidate for SDHI fungicides to control R. solani, warranting further investigation.

Efficient Screening of Pharmaceutical Cocrystals by Microspacing In-Air Sublimation.

Cocrystal screening and single-crystal growth remain the primary obstacles in the development of pharmaceutical cocrystals. Here, we present a new approach for cocrystal screening, microspacing in-air sublimation (MAS), to obtain new cocrystals and grow high-quality single crystals of cocrystals within tens of minutes. The method possesses the advantages of strong designable ability of devices, user-friendly control, and compatibility with materials, especially for the thermolabile molecules. A novel drug-drug cocrystal of favipiravir (FPV) with salicylamide (SAA) was first discovered by this method, which shows improved physiochemical properties. Furthermore, this method proved effective in cultivating single crystals of FPV-isonicotinamide (FPV-INIA), FPV-urea, FPV-nicotinamide (FPV-NIA), and FPV-tromethamine (FPV-Tro) cocrystals, and the structures of these cocrystals were determined for the first time. By adjusting the growth temperature and growth distance precisely, we also achieved single crystals of 10 different paracetamol (PCA) cocrystals and piracetam (PIR) cocrystals, which underscores the versatility and efficiency of this method in pharmaceutical cocrystal screening.

A novel two-dimensional Janus TiSiGeN4 monolayer with N vacancies for efficient photocatalytic nitrogen reduction.

The photocatalytic nitrogen reduction reaction (pNRR) is a clean technology that converts H2O and N2 into NH3 under environmental conditions using inexhaustible sunlight. Herein, we designed a novel two-dimensional (2D) Janus TiSiGeN4 structure and evaluated the pNRR performance of the structure with the presence of nitrogen vacancies at different positions using density functional theory (DFT) calculations. The intrinsic dipoles in the Janus TiSiGeN4 structure generate a built-in electric field, which promotes the migration of photogenerated electrons and holes towards the (001) and (00-1) surfaces, respectively, to achieve efficient charge separation. For the pNRR, the Si atoms exposed after the formation of top N vacancies can realize the efficient activation of N2 through the "acceptance-donation" mechanism, while the presence of middle N vacancies not only suppresses the hydrogen evolution reaction, a competition reaction, but also lowers the reaction barrier for the protonation of N atoms. The limiting potential of TiSiGeN4 with the coexistence of both top and middle N vacancies (TiSiGeN4-VN-mt) is as low as -0.44 V. In addition, the introduction of N vacancies generates defect levels, narrowing the band gap and improving the light response. This work provides theoretical guidance for the design of efficient pNRR photocatalysts under mild conditions.

[Retracted] Tissue­specific transplantation antigen P35B functions as an oncogene and is regulated by microRNA­125a­5p in lung cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunohistochemical data shown in Fig. 1A on p. 5, colony formation data shown in Figs. 2C, H and M and 6D on p. 6 and p. 10 respectively, the western blots in Fig. 2B, Transwell cell migration and invasion assay data in Fig. 3B, D and F, and immunofluorescence data in Fig. 4C had already appeared in previously published articles written by different authors at different research institutes (some of which have subsequently been retracted). Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 45: 72, 2021; DOI: 10.3892/or.2021.8023].

Quantitative measurement of acute myocardial infarction cardiac biomarkers by "All-in-One" immune microfluidic chip for early diagnosis of myocardial infarction.

Acute myocardial infarction (AMI) is a life-threatening condition with a narrow treatment window, necessitating rapid and accurate diagnostic methods. We present an "all-in-one" convenient and rapid immunoassay system that combines microfluidic technology with a colloidal gold immunoassay. A degassing-driven chip replaces a bulky external pump, resulting in a user-friendly and easy-to-operate immunoassay system. The chip comprises four units: an inlet reservoir, an immunoreaction channel, a waste pool, and an immunocomplex collection chamber, allowing single-channel flow for rapid and accurate AMI biomarker detection. In this study, we focused on cardiac troponin I (cTnI). With a minimal sample of just 4 µL and a total detection time of under 3 min, the chip enabled a quantitative visual analysis of cTnI concentration within a range of 0.5 âˆ¼ 60.0 ng mL-1. This all-in-one integrated microfluidic chip with colloidal gold immunoassay offers a promising solution for rapid AMI diagnosis. The system's portability, small sample requirement, and quantitative visual detection capabilities make it a valuable tool for AMI diagnostics.

Lactic acid bacteria reduce bacterial diarrhea in rabbits via enhancing immune function and restoring intestinal microbiota homeostasis.

BACKGROUND: Numerous previous reports have demonstrated the efficacy of Lactic acid bacteria (LAB) in promoting growth and preventing disease in animals. In this study, Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were isolated from the feces of healthy rabbits, and both strains showed good probiotic properties in vitro. Two strains (108CFU/ml/kg/day) were fed to weaned rabbits for 21 days, after which specific bacterial infection was induced to investigate the effects of the strains on bacterial diarrhea in the rabbits. RESULTS: Our data showed that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 interventions reduced the incidence of diarrhea and systemic inflammatory response, alleviated intestinal damage and increased antibody levels in animals. In addition, Enterococcus faecium ZJUIDS-R1 restored the flora abundance of Ruminococcaceae1. Ligilactobaciiius animalis ZJUIDS-R2 up-regulated the flora abundance of Adlercreutzia and Candidatus Saccharimonas. Both down-regulated the flora abundance of Shuttleworthia and Barnesiella to restore intestinal flora balance, thereby increasing intestinal short-chain fatty acid content. CONCLUSIONS: These findings suggest that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were able to improve intestinal immunity, produce organic acids and regulate the balance of intestinal flora to enhance disease resistance and alleviate diarrhea-related diseases in weanling rabbits.

Identification of Intersite Distance Effects in Au-Ag Single-Atom Alloy Catalysts Using Single Nanoparticle Collision Electrochemistry.

Regulating the atomic density of single-atom alloys (SAAs) promotes the potential to significantly enhance the electrocatalytic activity. However, conventional methods for study on the electrocatalytic performance of SAAs versus the intersite distance demand exhaustive experiments and characterization. Herein, we present a combinatorial synthesis and analysis method to investigate the intersite distance effect of SAA electrocatalysts. We employ single-nanoparticle collision electrochemistry to realize in situ electrodeposition of a precisely tunable Au atomic density onto individual parent Ag nanoparticles, followed by instantaneous electrocatalytic measurement of the newborn Au-Ag SAAs. In this work, the utility of our method is confirmed by the identification of intersite distance effects of Au-Ag SAAs toward the oxygen reduction reaction. When the site distance between two neighboring Au atoms is 1.9 nm, Au-Ag SAAs exhibit optimal activity. This work provides a simple and efficient method for screening other SAA electrocatalysts with ideal intersite distance at the single-nanoparticle level.

Semi or fully automatic tooth segmentation in CBCT images: a review.

Cone beam computed tomography (CBCT) is widely employed in modern dentistry, and tooth segmentation constitutes an integral part of the digital workflow based on these imaging data. Previous methodologies rely heavily on manual segmentation and are time-consuming and labor-intensive in clinical practice. Recently, with advancements in computer vision technology, scholars have conducted in-depth research, proposing various fast and accurate tooth segmentation methods. In this review, we review 55 articles in this field and discuss the effectiveness, advantages, and disadvantages of each approach. In addition to simple classification and discussion, this review aims to reveal how tooth segmentation methods can be improved by the application and refinement of existing image segmentation algorithms to solve problems such as irregular morphology and fuzzy boundaries of teeth. It is assumed that with the optimization of these methods, manual operation will be reduced, and greater accuracy and robustness in tooth segmentation will be achieved. Finally, we highlight the challenges that still exist in this field and provide prospects for future directions.

Claudin-7 is essential for the maintenance of colonic stem cell homoeostasis via the modulation of Wnt/Notch signalling.

Intestinal stem cells (ISCs) play a crucial role in the continuous self-renewal and recovery of the intestinal epithelium. In previous studies, we have revealed that the specific absence of Claudin-7 (Cldn-7) in intestinal epithelial cells (IECs) can lead to the development of spontaneous colitis. However, the mechanisms by which Cldn-7 maintains homeostasis in the colonic epithelium remain unclear. Therefore, in the present study, we used IEC- and ISC-specific Cldn-7 knockout mice to investigate the regulatory effects of Cldn-7 on colonic Lgr5+ stem cells in the mediation of colonic epithelial injury and repair under physiological and inflammatory conditions. Notably, our findings reveal that Cldn-7 deletion disrupts the self-renewal and differentiation of colonic stem cells alongside the formation of colonic organoids in vitro. Additionally, these Cldn-7 knockout models exhibited heightened susceptibility to experimental colitis, limited epithelial repair and regeneration, and increased differentiation toward the secretory lineage. Mechanistically, we also established that Cldn-7 facilitates the proliferation, differentiation, and organoid formation of Lgr5+ stem cells through the maintenance of Wnt and Notch signalling pathways in the colonic epithelium. Overall, our study provides new insights into the maintenance of ISC function and colonic epithelial homoeostasis.

Rolling bearing fault diagnosis based on fine-grained multi-scale Kolmogorov entropy and WOA-MSVM.

In allusion to solve the issue of fault diagnosis for bearing and other rotatory machinery, a technique based on fined-grained multi-scale Kolmogorov entropy and whale optimized multi-class support vector machine (abbreviated as FGMKE-WOA-MSVM) is proposed. Firstly, vibration signals are decomposed by fine-grained multi-scale decomposition, and the Kolmogorov entropy of the sub-signals at different analysis scales is calculated as the multi-dimension feature vector, which quantitatively characterize the complexity of the signal at multi-scales. Aiming at the problem of sensitive parameters selection for multi-class support vector machine model (abbreviated as MSVM), the whale optimization algorithm (abbreviated as WOA) is introduced to optimize the penalty factor and kernel function parameter, and constructing optimal WOA-MSVM model. Finally, an instance analysis is carried out with Jiangnan University bearing datasets to verify the effectiveness and superiority of this technique. The results show that compared with different feature vectors and models such as K nearest neighbors (abbreviated as KNN) and Decision Tree (abbreviated as RF), the proposed technique is superior with fast computation speed and high diagnostic efficiency.

XPO1 inhibition displays anti-leukemia efficacy against DNMT3A-mutant acute myeloid leukemia via downregulating glutathione pathway.

Acute myeloid leukemia (AML) patients with DNA methyltransferase 3A (DNMT3A) mutation display poor prognosis, and targeted therapy is not available currently. Our previous study identified increased expression of Exportin1 (XPO1) in DNMT3AR882H AML patients. Therefore, we further investigated the therapeutic effect of XPO1 inhibition on DNMT3AR882H AML. Three types of DNMT3AR882H AML cell lines were generated, and XPO1 was significantly upregulated in all DNMT3AR882H cells compared with the wild-type (WT) cells. The XPO1 inhibitor selinexor displayed higher potential in the inhibition of proliferation, promotion of apoptosis, and blockage of the cell cycle in DNMT3AR882H cells than WT cells. Selinexor also significantly inhibited the proliferation of subcutaneous tumors in DNMT3AR882H AML model mice. Primary cells with DNMT3A mutations were more sensitive to selinexor in chemotherapy-naive AML patients. RNA sequencing of selinexor treated AML cells revealed that the majority of metabolic pathways were downregulated after selinexor treatment, with the most significant change in the glutathione metabolic pathway. Glutathione inhibitor L-Buthionine-(S, R)-sulfoximine (BSO) significantly enhanced the apoptosis-inducing effect of selinexor in DNMT3AWT/DNMT3AR882H AML cells. In conclusion, our work reveals that selinexor displays anti-leukemia efficacy against DNMT3AR882H AML via downregulating glutathione pathway. Combination of selinexor and BSO provides novel therapeutic strategy for AML treatment.

Epidemiology of tuberculosis among children in Beijing, China, 2012-2021.

Data on epidemiology trends of paediatric tuberculosis (TB) are limited in China. So, we investigated the clinical and epidemiological profiles in diagnosed TB disease and TB infection patients at Beijing Children's Hospital. Of 3 193 patients, 51.05% had pulmonary TB (PTB) and 15.16% had extrapulmonary TB (EPTB). The most frequent forms of EPTB were TB meningitis (39.05%), pleural TB (29.75%), and disseminated TB (10.33%). PTB patients were significantly younger and associated with higher hospitalization frequency. Children aged 1-4 years exhibited higher risk of PTB and TB meningitis, and children aged 5-12 years had higher risk of EPTB. The proportion of PTB patients increased slightly from 40.9% in 2012 to 65% in 2019, and then decreased to 17.8% in 2021. The percentage of EPTB cases decreased from 18.3% in 2012 to 15.2% in 2019, but increased to 16.4% in 2021. Among EPTB cases, the largest increase was seen in TB meningitis. In conclusion, female and young children had higher risk of PTB in children. TB meningitis was the most frequent forms of EPTB among children, and young children were at high risk of TB meningitis. The distribution of different types of EPTB differed by age.

The relationship of ALPK1, hyaluronic acid and M1 macrophage polarization in the temporomandibular joint synovitis.

M1 macrophage polarization and synovitis play an important role in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA). Reduced molecular weight of hyaluronic acid (HA) in synovial fluid of patients with TMJOA. In addition, high molecular weight hyaluronic acid (HMW-HA) is often used clinically to treat TMJ inflammation. As a pattern recognition receptor of the cytoplasm, ALPK1 was found to be pro-inflammatory in a variety of diseases. However, the relationship of ALPK1, HA and M1 macrophage polarization in TMJ synovitis remains unclear. We aimed to investigate the role of ALPK1 and HA in macrophage polarization and TMJ synovitis and the underlying mechanisms. The results demonstrated that ALPK1 was highly upregulated in the synovial macrophages in the inflamed TMJ synovium of patients. Low molecular weight hyaluronic acid (LMW-HA) promoted the expression of ALPK1 and M1 macrophage-associated genes. Besides, rhALPK1 promoted the expression of M1 macrophage-associated factors and the nuclear translocation of PKM2. Furthermore, ALPK1 knockout mice exhibited limited infiltration of macrophages and decreased expression levels of M1 macrophage-associated genes in CFA-induced TMJ synovitis. While HMW-HA inhibited the expression of ALPK1 and M1 macrophage polarization. Our results elucidated that ALPK1 promoted TMJ synovitis by promoting nuclear PKM2-mediated M1 macrophage polarization, whereas HMW-HA inhibited the expression of ALPK1 as well as M1 macrophage polarization.

Integrated bioinformatics analysis of ferroptosis-related gene signature in inflammation and immunity in intervertebral disc degeneration.

Ferroptosis has recently been shown to play a significant role in the progression of intervertebral disk degeneration (IDD), although the underlying mechanism is still unknown. The objective of this work was to use stringent bioinformatic techniques to clarify the crucial roles played by genes associated with ferroptosis in the emergence of IDD. For additional study, the microarray data pertinent to the IDD were acquired from the Gene Expression Omnibus database. The ferroptosis-related and IDD-related genes (FIDDRGs) were identified using a variety of bioinformatic techniques, which were also used to carry out function enrichment analysis, protein-protein correlation analysis, build the correlation regulatory network, and examine the potential connections between ferroptosis and immune abnormalities and inflammatory responses in IDD. A total of 16 FIDDRGs were eliminated for the further function enrichment analysis, and 10 hub FIDDRGs were chosen to build the correlation regulatory network. Hub FIDDRGs were shown to be highly associated with M2 macrophages and hub inflammatory response-related genes in IDD. When seen as a whole, our findings can give fresh perspectives on the mechanistic studies of ferroptosis in the emergence of IDD and new prospective targets for the therapeutic approaches.

4-Hydroxyphenylpyruvate Dioxygenase-Like predicts the prognosis and the immunotherapy response of cancers: a pan-cancer analysis.

The 4-Hydroxyphenylpyruvate Dioxygenase-Like (HPDL) protein plays a crucial role in safeguarding cells from oxidative stress by orchestrating metabolic reprogramming. New research suggests that HPDL is considerably increased in pancreatic ductal adenocarcinoma, although its impact on cancer immunotherapy is still unclear. Pancancer transcriptional data were obtained from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression datasets. The cBioPortal webtool was utilized to examine genomic changes in different cancer types. The prognostic significance of HPDL in pancancer was evaluated using univariate Cox regression analysis. Extensive utilization of the CTRP and PRISM databases was performed to forecast potential medications that specifically target HPDL in LUAD. In summary, studies were conducted to evaluate the impact of HPDL on the proliferation and movement of LUAD cells using loss-of-function experiments. HPDL is expressed excessively in a wide variety of cancer types, indicating its prognostic and predictive value. Moreover, we emphasized the strong correlation between HPDL and indicators of immune stimulation, infiltration of immune cells, and expression of immunoregulators. The remarkable finding of the HPDL was its capacity to precisely anticipate responses to cancer therapies using anti-PDL1 and anti-PD1 antibodies among individuals. Moreover, HPDL can function as a predictive marker for specific inhibitors in instances of cancer. Suppression of HPDL resulted in reduced growth and movement of LUAD cells. To summarize, our results suggest that HPDL acts as a prospective predictor of outcomes and a positive indication of response to immunotherapy in patients undergoing treatment with immune checkpoint inhibitors (ICIs).

Nitrogen fertiliser-domesticated microbes change the persistence and metabolic profile of atrazine in soil.

Pesticides and fertilisers are frequently used and may co-exist on farmlands. The overfertilisation of soil may have a profound influence on pesticide residues, but the mechanism remains unclear. The effects of chemical fertilisers on the environmental behaviour of atrazine and their underlying mechanisms were investigated. The present outcomes indicated that the degradation of atrazine was inhibited and the half-life was prolonged 6.0 and 7.6 times by urea and compound fertilisers (NPK) at 1.0 mg/g (nitrogen content), respectively. This result, which was confirmed in both sterilised and transfected soils, was attributed to the inhibitory effect of nitrogen fertilisers on soil microorganisms. The abundance of soil bacteria was inhibited by nitrogen fertilisers, and five families of potential atrazine degraders (Micrococcaceae, Rhizobiaceae, Bryobacteraceae, Chitinophagaceae, and Sphingomonadaceae) were strongly and positively (R > 0.8, sig < 0.05) related to the decreased functional genes (atzA and trzN), which inhibited hydroxylation metabolism and ultimately increased the half-life of atrazine. In addition, nitrogen fertilisers decreased the sorption and vertical migration behaviour of atrazine in sandy loam might increase the in-situ residual and ecological risk. Our findings verified the weakened atrazine degradation with nitrogen fertilisers, providing new insights into the potential risks and mechanisms of atrazine in the context of overfertilisation.

Design, synthesis and antitumor activity of 2-substituted quinazoline-4-amine derivatives.

Werner (WRN) syndrome protein is a multifunctional enzyme with helicase, ATPase, and exonuclease activities that are necessary for numerous DNA-related transactions in the human cell. Recent studies identified WRN as a synthetic lethal target in cancers. In this study, a series of new N-arylquinazoline-4-amine analogs were designed and synthesized based on structure optimization of quinazoline. The structures of the thirty-two newly synthesized compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. The anticancer activity in vitro against chronic myeloid leukemia cells (K562), non-small cell lung cancer cells (A549), human prostate cancer cells (PC3), and cervical cancer cells (HeLa) of the target compounds was evaluated. Among them, the inhibition ratio of compounds 17d, 18a, 18b, 11 and 23a against four cancer cells at 5 µM concentration were more than 50 %. The IC50 values of compounds 18a and 18b were 0.3 ± 0.01 µM and 0.05 ± 0.02 µM in K562 cells respectively, compared with HeLa and A549 cells, 18a and 18b were more sensitive to K562 cells. In addition, the PC3 cells with WRN overexpression (PC3-WRN) was constructed, 18a and 18b and 23a were more sensitive to PC3-WRN cells compared with the control group cells (PC3-NC). Then, the cell viability of the novel WRN inhibitors were further assessed by colony formation assay. Compared with PC3-NC cells, 18b and 23a had obvious inhibitory effect on PC3-WRN cell at 1000 nM. In summary, these results indicated that the compounds 18b and 23a could be WRN protein inhibitor with potent anticancer properties in vitro.

Construction of a novel mRNA-miRNA-lncRNA/circRNA triple subnetwork associated with immunity and aging in intervertebral disc degeneration.

OBJECTIVE: Intervertebral disk degeneration (IVDD) is one of the most common causes of low back pain. However, in the etiology of IVDD, the specific method by which nucleus pulposus (NP) cell senescence and the immune response induce disease is uncertain. METHODS: Gene Expression Omnibus database was used to find differentially expressed genes (DEGs), differentially expressed miRNAs (DE miRNAs), differentially expressed lncRNAs (DE lncRNAs), and differentially expressed circRNAs (DE circRNAs). Functional enrichment analysis was performed through Enrichr database. Potential regulatory miRNAs, lncRNAs and circRNAs of mRNAs were predicted by ENCORI and circBank, respectively. RESULTS: We identified 198 upregulated and 131 downregulated genes, 39 upregulated and 22 downregulated miRNAs, 2152 upregulated and 564 downregulated lncRNAs, and 352 upregulated and 279 downregulated circRNAs as DEGs, DE miRNAs, DE lncRNAs, DE circRNAs, respectively. Functional enrichment analysis revealed that they were significantly enriched in Toll-like receptor signaling route and the NF-kappa B signaling pathway. An mRNA-miRNA-lncRNA/circRNA network linked to the pathogenesis of NP cells in IVDD was constructed based on node degree and differential expression level. Eight immune-related DEGs (6 upregulated and 2 downregulated genes) and five aging-related DEGs (3 upregulated and 2 downregulated genes) were identified in the critical network. CONCLUSION: We established a novel immune-related and aging-related triple regulatory network of mRNA-miRNA-lncRNA/circRNA ceRNA, among which all RNAs may be utilized as the pathogenesis biomarker of NP cells in IVDD.

Bioinspired, surfactant-free, dual-layer asymmetric structures based on polysaccharides, gelatin, and tannic acid for potential applications in biomedicine.

The formation of dual-layer asymmetric porous structures in surfactant-based systems is significantly influenced by emulsions. Surfactants self-assemble to alter the conformational arrangement of polysaccharides, while gravity disrupts the initial uniformity of the established equilibrium droplet concentration gradient in the emulsion, thus achieving delamination. Specifically, high-speed rotation and non-instantaneous freezing allow the gelatin solution to form two different states of foam layers. The integrated dual-layer asymmetric porous structure, composed of polysaccharides and tannic acid, is constructed with gelatin as a skeleton and surfactant. This innovative approach eliminates the need to consider the toxicity of chemically synthesized surfactants and expands the concept of gelatin utilization. This intriguing structure exhibits a variety of desirable characteristics within 30 days (e.g., tailorable performance, ultrarapid antioxidant activity, efficient antibacterial activity, low differential blood clotting index, and good hemocompatibility and cytocompatibility), suggesting its potential as a valuable reference for applying hierarchical porous structures, thereby offering more formulation flexibility for biomaterials with adjustable properties.