Ultrafast electron transfer at the In2O3/Nb2O5 S-scheme interface for CO2 photoreduction.

Constructing S-scheme heterojunctions proves proficient in achieving the spatial separation of potent photogenerated charge carriers for their participation in photoreactions. Nonetheless, the restricted contact areas between two phases within S-scheme heterostructures lead to inefficient interfacial charge transport, resulting in low photocatalytic efficiency from a kinetic perspective. Here, In2O3/Nb2O5 S-scheme heterojunctions are fabricated through a straightforward one-step electrospinning technique, enabling intimate contact between the two phases and thereby fostering ultrafast interfacial electron transfer (<10 ps), as analyzed via femtosecond transient absorption spectroscopy. As a result, powerful photo-electrons and holes accumulate in the Nb2O5 conduction band and In2O3 valence band, respectively, exhibiting extended long lifetimes and facilitating their involvement in subsequent photoreactions. Combined with the efficient chemisorption and activation of stable CO2 on the Nb2O5, the resulting In2O3/Nb2O5 hybrid nanofibers demonstrate improved photocatalytic performance for CO2 conversion.

Ionic Nitrogen-Doped Carbon Dots as Nonpolar Lubricant Additives at Low Effective Addition.

The poor compatibility with nonpolar lubricant still hinders the application of carbon dots (CDs) in lubrication. In addition, research proves that the existence of ionic structure and active groups on CDs are conducive to their lubricity. In order to obtain the ionic structures and good oil compatibility synchronously, a kind of ionic nitrogen-doped CDs (NCDs) was synthesized via the alkylation of nitrogen in NCDs and anion exchange. The new material could exhibit good tribological performance as poly alpha olefins (PAO4) additives with low addition. Moreover, an ionic liquid, [N44HH][DEHP], with the same anion was chosen as a comparison to investigate the role of NCD cations. The surface analyses demonstrate that NCD cations and phosphate ester anions adsorb on the friction interface to play a synergistic lubrication role during the friction process, which could generate a superior carbon-based tribofilm.

The combination of tumor mutational burden and T-cell receptor repertoire predicts the response to immunotherapy in patients with advanced non-small cell lung cancer.

Tumor mutational burden (TMB) and T-cell receptor (TCR) might predict the response to immunotherapy in patients with non-small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB-and-TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set (n = 17) and validation set (n = 21). A higher TMR score was associated with better response and longer progression-free survival to immunotherapy in both the discovery set and validation set. The performance of TMR score was confirmed in the two external validation cohorts of 225 NSCLC patients and 306 NSCLC patients. Tumors with higher TMR scores were more likely to combine with LRP1B gene mutation (p = 0.027) and top 1% CDR3 sequences (p = 0.001). Furthermore, LRP1B allele frequency was negatively correlated with the top 1% CDR3 sequences (r = -0.55, p = 0.033) and positively correlated with tumor shrinkage (r = 0.68, p = 0.007). The TMR score could serve as a potential predictive biomarker for the response to immunotherapy in advanced NSCLC.

Mutational characteristics and clinical outcomes for lung adenocarcinoma with EGFR germline mutations.

BACKGROUND: Germline mutations driving lung cancer have been infrequently reported in literature, with EGFR T790M being a known germline mutation identified in 1% of NSCLC. Typically, a somatic EGFR mutation is acquired to develop lung adenocarcinoma. Osimertinib has become standard-of-care treatment for EGFR T790M-positive lung cancer. METHODS: We perform a retrospective analysis through the Lung Cancer Moon Shot GEMINI database at the UT MD Anderson Cancer Center. Of the patients that underwent cfDNA analysis, germline mutations were identified by those with high variant allelic fraction (VAF) approximating 50%, followed by further confirmation on genetic testing. RESULTS: We identified 22 patients with germline EGFR mutations, with the majority harboring an EGFR T790M mutation (95.5%) and EGFR L858R somatic mutation (50%). Notably, most patients were female (86.4%), non-smokers (81.8%), Caucasian (86.4%), have family history of lung cancer (59.1%), and stage IV at diagnosis (72.7%). A distinct radiographic pattern of small multifocal ground-glass pulmonary nodules was observed in the majority of our cohort (72.7%). Among the 18 with advanced-stage NSCLC, 12 (66.7%) were treated with first-line osimertinib, demonstrating a median PFS of 16.9 months (95% CI; 6.3-NR). Others were treated with first-line afatinib (11.1%) or chemotherapy (22.2%). Among the 17 patients treated with osimertinib (in first or second-line), mPFS was 20.4 months (95% CI; 6.3-NR) and mOS was 82.0 months (95% CI; 28.4-NR). CONCLUSION: Based on our institutional cohort, NSCLC driven by EGFR germline mutations occur more frequently in non-smoking, Caucasian females with multi-focal pulmonary nodules radiographically. Osimertinib for advanced germline EGFR-mutated NSCLC renders similar PFS compared to somatic T790M EGFR-mutated NSCLC.

CoCo-ST: Comparing and Contrasting Spatial Transcriptomics data sets using graph contrastive learning.

Traditional feature dimension reduction methods have been widely used to uncover biological patterns or structures within individual spatial transcriptomics data. However, these methods are designed to yield feature representations that emphasize patterns or structures with dominant high variance, such as the normal tissue spatial pattern in a precancer setting. Consequently, they may inadvertently overlook patterns of interest that are potentially masked by these high-variance structures. Herein we present our graph contrastive feature representation method called CoCo-ST (Comparing and Contrasting Spatial Transcriptomics) to overcome this limitation. By incorporating a background data set representing normal tissue, this approach enhances the identification of interesting patterns in a target data set representing precancerous tissue. Simultaneously, it mitigates the influence of dominant common patterns shared by the background and target data sets. This enables discerning biologically relevant features crucial for capturing tissue-specific patterns, a capability we showcased through the analysis of serial mouse precancerous lung tissue samples.

Plasmonic Near-Infrared-Response S-Scheme ZnO/CuInS2 Photocatalyst for H2O2 Production Coupled with Glycerin Oxidation.

Solar fuel synthesis is intriguing because solar energy is abundant and this method compensates for its intermittency. However, most photocatalysts can only absorb UV-to-visible light, while near-infrared (NIR) light remains unexploited. Surprisingly, the charge transfer between ZnO and CuInS2 quantum dots (QDs) can transform a NIR-inactive ZnO into a NIR-active composite. This strong response is attributed to the increased concentration of free charge carriers in the p-type semiconductor at the interface after the charge migration between ZnO and CuInS2, enhancing the localized surface plasmon resonance (LSPR) effect and the NIR response of CuInS2. As a paradigm, this ZnO/CuInS2 heterojunction is used for H2O2 production coupled with glycerin oxidation and demonstrates supreme performance, corroborating the importance of NIR response and efficient charge transfer. Mechanistic studies through contact potential difference (CPD), Hall effect test, and finite element method (FEM) calculation allow for the direct correlation between the NIR response and charge transfer. This approach bypasses the general light response issues, thereby stepping forward to the ambitious goal of harnessing the entire solar spectrum.

Knowledge and attitudes toward mild traumatic brain injury among patients and family members.

Introduction: Mild traumatic brain injury (mTBI) is a prevalent health issue with significant effects on patients' lives. Understanding and attitudes toward mTBI among patients and their families can influence management and outcomes. This study aimed to assess knowledge and attitudes toward mTBI in these groups. Methods: A cross-sectional study was conducted at Zhejiang Hospital from July 1, 2023, to September 30, 2023. Patients with mTBI and their family members participated. Data were collected via an online questionnaire covering demographic information and mTBI knowledge and attitudes. Knowledge scores ranged from 0 to 20 and attitude scores from 8 to 40. Multivariate logistic regression identified factors influencing these scores. Results: A total of 573 valid questionnaires were analyzed (289 males, 50.44%; 284 females, 49.56%). Among respondents, 258 (45.03%) had experienced a concussion. Mean knowledge and attitude scores were 11.00 ± 2.75 and 27.78 ± 4.07, respectively. Monthly per capita income of 5,000-10,000 RMB was negatively associated with knowledge and attitude scores (ß = 0.160, 95% CI: [3.245 to 0.210], P = 0.026). Middle school education decreased the likelihood of positive attitudes toward mTBI (OR = 0.378, 95% CI: [0.1630.874], P = 0.023). mTBI due to falls was associated with increased likelihood of positive attitudes (OR = 3.588, 95% CI: [1.274-10.111], P = 0.016). Discussion: Significant gaps in knowledge and attitudes toward mTBI exist among patients and their families, influenced by income and education levels. Personal experience with mTBI from falls correlates with more positive attitudes. These findings highlight the need for targeted educational interventions to improve understanding and attitudes, ultimately enhancing patient care and management. Comprehensive, accessible mTBI education is crucial for fostering positive attitudes and better knowledge among patients and their families.

The prognostic significance of preoperative platelet-to-lymphocyte ratio and interleukin-6 level in non-muscle invasive bladder cancer.

BACKGROUND: Non-muscle invasive bladder cancer (NMIBC) is the most prevalent type of bladder cancer, typically associated with a favorable prognosis and a risk of recurrence during the follow-up period. Inflammatory markers have been used to predict prognosis in various cancer types. The aim of this study was to explore the prognostic value of the readily accessible inflammatory markers, platelet-to-lymphocyte ratio (PLR) and interleukin-6 (IL-6), in NMIBC. METHODS: The study comprised a retrospective analysis of clinical data collected from NMIBC patients diagnosed between October 2018 and October 2020. PLR was calculated using the routine preoperative blood test results, and preoperative IL-6 levels were recorded. Receiver operating characteristic (ROC) curves were generated for PLR and IL-6 level and the optimal cut-off values were determined using Youden's index. Survival curves were generated to evaluate the association between PLR and IL-6, and recurrence-free survival (RFS), and univariate and multivariate analysis were performed using the Cox proportional hazards regression model. A nomogram and calibration curve were generated to assess the clinical significance of the model. RESULTS: The ROC curves demonstrated that PLR and IL-6 levels were significantly associated with tumor pathology grade, with area under the curve (AUC) values of 0.833 (95% CI 0.757, 0.910) for PLR and 0.724 (95% CI 0.622, 0.825) for IL-6 levels. PLR and IL-6 levels were also positively associated with tumor recurrence, with AUC values of 0.647 (95% CI 0.538, 0.756) and 0.846 (95% CI 0.769, 0.924), respectively. The survival curves indicated that patients with high PLR and high IL-6 levels had shorter RFS than those with low PLR and low IL-6 level (P < 0.01). Univariate Cox proportional hazards regression analysis showed that age, tumor size, tumor number, pathological grade, PLR and IL-6 were potential risk factors for NMIBC recurrence. Multivariate analysis further revealed that tumor number, smoking, PLR, and IL-6 were independent risk factors for NMIBC recurrence (P < 0.05). CONCLUSIONS: Preoperative peripheral blood inflammatory markers (PLR and IL-6) are useful predictors of RFS in NMIBC patients at the time of initial diagnosis. High PLR and high IL-6 were identified as independent risk factors for tumor recurrence and could serve as potential biological markers for prediction of NMIBC recurrence.

The evolution of lung adenocarcinoma precursors is associated with chromosomal instability and transition from innate to adaptive immune response/evasion.

Studying lung adenocarcinoma (LUAD) early carcinogenesis is challenging, primarily due to the lack of LUAD precursors specimens. We amassed multi-omics data from 213 LUAD and LUAD precursors to identify molecular features underlying LUAD precancer evolution. We observed progressively increasing mutations, chromosomal aberrations, whole genome doubling and genomic instability from precancer to invasive LUAD, indicating aggravating chromosomal instability (CIN). Telomere shortening, a crucial genomic alteration linked to CIN, emerged at precancer stage. Moreover, later-stage lesions demonstrated increasing cancer stemness and decreasing alveolar identity, suggesting epithelial de-differentiation during early LUAD carcinogenesis. The innate immune cells progressively diminished from precancer to invasive LUAD, concomitant with a gradual recruitment of adaptive immune cells (except CD8+ and gamma-delta T cells that decreased in later stages) and upregulation of numerous immune checkpoints, suggesting LUAD precancer evolution is associated with a shift from innate to adaptive immune response and immune evasion mediated by various mechanisms.

Duloxetine protected indomethacin-induced gastric mucosal injury by increasing serotonin-dependent RANTES expression and activating PI3K-AKT-VEGF pathway.

Antidepressant duloxetine has been shown protective effect on indomethacin-induced gastric ulcer, which was escorted by inflammation in the gastric mucosa. Cytokines are the principal mediators of inflammation. Thus, by screening the differential expression of cytokines in the gastric mucosa using cytokine array at 3 h after indomethacin exposure, when the gastric ulcer began to format, we found that indomethacin increased cytokines which promoted inflammation responses, whereas duloxetine decreased pro-inflammatory cytokines increased by indomethacin and increased RANTES expression. RANTES was consistently increased by pretreated with both 5 mg/kg and 20 mg/kg duloxetine at 3 h and 6 h after indomethacin exposure in male rats. Selective blockade of RANTES-CCR5 axis by a functional antagonist Met-RANTES or a CCR5 antagonist maraviroc suppressed the protection of duloxetine. Considering the pharmacologic action of duloxetine on reuptake of monoamine neurotransmitters, we examined the serotonin (5-HT), norepinephrine and dopamine contents in the blood and discovered 20 mg/kg duloxetine increased 5-HT levels in platelet-poor plasma, while treatment with 5-HT promoted expression of RANTES in the gastric mucosa and alleviated the indomethacin-induced gastric injury. Furthermore, duloxetine activated PI3K-AKT-VEGF signaling pathway, which was regulated by RANTES-CCR5, and selective inhibitor of VEGF receptor axitinib blocked the prophylactic effect of duloxetine. Furthermore, duloxetine also protected gastric mucosa from indomethacin in female rats, and RANTES was increased by duloxetine after 6 h after indomethacin exposure too. Together, our results identified the role of cytokines, particularly RANTES, and the underlying mechanisms in gastroprotective effect of duloxetine against indomethacin, which advanced our understanding in inflammatory modulation by monoamine-based antidepressants.

Joint multi-omics discriminant analysis with consistent representation learning using PANDA.

Integrative multi-omics analysis provides deeper insight and enables better and more realistic modeling of the underlying biology and causes of diseases than does single omics analysis. Although several integrative multi-omics analysis methods have been proposed and demonstrated promising results in integrating distinct omics datasets, inconsistent distribution of the different omics data, which is caused by technology variations, poses a challenge for paired integrative multi-omics methods. In addition, the existing discriminant analysis-based integrative methods do not effectively exploit correlation and consistent discriminant structures, necessitating a compromise between correlation and discrimination in using these methods. Herein we present PAN-omics Discriminant Analysis (PANDA), a joint discriminant analysis method that seeks omics-specific discriminant common spaces by jointly learning consistent discriminant latent representations for each omics. PANDA jointly maximizes between-class and minimizes within-class omics variations in a common space and simultaneously models the relationships among omics at the consistency representation and cross-omics correlation levels, overcoming the need for compromise between discrimination and correlation as with the existing integrative multi-omics methods. Because of the consistency representation learning incorporated into the objective function of PANDA, this method seeks a common discriminant space to minimize the differences in distributions among omics, can lead to a more robust latent representations than other methods, and is against the inconsistency of the different omics. We compared PANDA to 10 other state-of-the-art multi-omics data integration methods using both simulated and real-world multi-omics datasets and found that PANDA consistently outperformed them while providing meaningful discriminant latent representations. PANDA is implemented using both R and MATLAB, with codes available at https://github.com/WuLabMDA/PANDA.

Specific surface area of mannitol rather than particle size dominant the dissolution rate of poorly water-soluble drug tablets: A study of binary mixture.

The dissolution behavior of tablets, particularly those containing poorly water-soluble drugs, is a critical factor in determining their absorption and therapeutic efficacy. Traditionally, the particle size of excipients has been considered a key property affecting tablet dissolution. However, lurasidone hydrochloride (LH) tablets prepared by similar particle size mannitol, namely M200 (D90 = 209.68 ±â€¯1.42 µm) and 160C (D90 = 195.38 ±â€¯6.87 µm), exhibiting significant differences in their dissolution behavior. In order to find the fundamental influential factors of mannitol influencing the dissolution of LH tablets, the properties (particle size, water content, true density, bulk density, tapped density, specific surface area, circularity, surface free energy, mechanical properties and flowability) of five grades mannitol including M200 and 160C were investigated. Principal component analysis (PCA) was used to establish a relationship between mannitol properties and the dissolution behavior of LH. The results demonstrated that specific surface area (SSA) emerged as the key property influencing the dissolution of LH tablets. Moreover, our investigation based on the percolation theory provided further insights that the SSA of mannitol influences the probability of LH-LH bonding and LH infinite cluster formation, resulting in the different percolation threshold states, then led to different dissolution behaviors. Importantly, it is worth noting that these findings do not invalidate previous conclusions, as reducing particle size generally increases SSA, thereby affecting the percolation threshold and dissolution behavior of LH. Instead, this study provides a deeper understanding of the underlying role played by excipient SSA in the dissolution of drug tablets. This study provides valuable guidance for the development of novel excipients aimed at improving drug dissolution functionality.

Novel phenanthrene/bibenzyl trimers from the tubers of Bletilla striata attenuate neuroinflammation via inhibition of NF-κB signaling pathway.

Five novel (9,10-dihydro) phenanthrene and bibenzyl trimers, as well as two previously identified biphenanthrenes and bibenzyls, were isolated from the tubers of Bletilla striata. Their structures were elucidated through comprehensive analyses of NMR and HRESIMS spectroscopic data. The absolute configurations of these compounds were determined by calculating rotational energy barriers and comparison of experimental and calculated ECD curves. Compounds 5b and 6 exhibited inhibitory effects on LPS-induced NO production in BV-2 cells, with IC50 values of 12.59 ± 0.40 and 15.59 ± 0.83 µmol·L-1, respectively. A mechanistic study suggested that these compounds may attenuate neuroinflammation by reducing the activation of the AKT/IκB/NF-κB signaling pathway. Additionally, compounds 3a, 6, and 7 demonstrated significant PTP1B inhibitory activities, with IC50 values of 1.52 ± 0.34, 1.39 ± 0.11, and 1.78 ± 0.01 µmol·L-1, respectively. Further investigation revealed that compound 3a might inhibit LPS-induced PTP1B overexpression and NF-κB activation, thereby mitigating the neuroinflammatory response in BV-2 cells.

Clinical implications and mechanism of CST1 in gastric carcinoma based on database screening.

Gastric cancer (GC) remains one of the most common malignant tumours worldwide, with extremely high morbidity and mortality rates. An in-depth understanding of the pathogenesis of GC is key to the future diagnosis and treatment of GC. In this study, we analysed the differentially expressed genes (DEGs) in gastric carcinoma (GC) through GEO database and their clinical implications, with the aim of providing clinical reference and guidance. We selected the GSE118916 dataset for bioinformatics analysis and identified a total of 3231 DEGs. Keywords, including extracellular region, vesicle, protein digestion and absorption, ECM-receptor interaction, etc., of DEGs can be seen by the GO and KEGG enrichment analysis. The online database determined up-regulated CST1 in GC and some other tumors, as well as a close connection between CST1 with patient prognosis. Subsequently, we collected a number of GC clinical cases and examined the expression of CST1, which was seen to be highly expressed in GC, with a favorable diagnostic effect on the occurrence of GC (P<0.05) and a strong correlation with TNM stage, tumor invasion, tumor diameter and differentiation (P<0.05). In other words, CST1 is closely related to the occurrence and development of GC, and has the potential to be a breakthrough in the diagnosis and treatment of GC in the future.

Molecularly Tunable Heterostructured Co-Polymers Containing Electron-Deficient and -Rich Moieties for Visible-Light and Sacrificial-Agent-Free H2O2 Photosynthesis.

As an alternative to hydrogen peroxide (H2O2) production by complex anthraquinone oxidation process, photosynthesis of H2O2 from water and oxygen without sacrificial agents is highly demanded. Herein, a covalently connected molecular heterostructure is synthesized via sequential C-H arylation and Knoevenagel polymerization reactions for visible-light and sacrificial-agent-free H2O2 synthesis. The subsequent copolymerization of the electron-deficient benzodithiophene-4,8-dione (BTD) and the electron-rich biphenyl (B) and p-phenylenediacetonitrile (CN) not only expands the π-conjugated domain but also increases the molecular dipole moment, which largely promotes the separation and transfer of the photoinduced charge carriers. The optimal heterostructured BTDB-CN0.2 manifested an impressive photocatalytic H2O2 production rate of 1920 µmol g-1 h-1, which is 2.2 and 11.6 times that of BTDB and BTDCN. As revealed by the femtosecond transient absorption (fs-TA) and theoretical calculations, the linkage serves as a channel for the rapid transfer of photogenerated charge carriers, enhancing the photocatalytic efficiency. Further, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) uncovers that the oxygen reduction reaction occurs through the step one-electron pathway and the mutual conversion between C=O and C-OH with the anchoring of H+ during the catalysis favored the formation of H2O2. This work provides a novel perspective for the design of efficient organic photocatalysts.

Enhancing the acidic oxygen evolution reaction performance of RuO2-TiO2by a reduction-oxidation process.

As a promising alternative to Ir based acidic oxygen evolution reaction (OER) catalysts, Ru suffers from severe fading issues. Supporting it on robust oxides such as TiO2is a simple and effective way to enhance its lifetime. Here, we find that a simple reduction-oxidation process can further improve both activity and stability of RuO2-TiO2composites at high potentials. In this process, the degree of oxidation was carefully controlled to form Ru/RuO2heterostructure to improve OER activity. Moreover, due to the oxophilicity difference of Ru and Ti, the structure of catalysts was changed from supported to embedded, which enhanced the protective effect of TiO2and mitigated the dissolution of Ru element in acidic electrolyte, making as-prepared Ru/RuO2-TiO2with better durability at all tested potentials.

Design of Inhibitors Targeting Chitin-Degrading Enzymes by Bioisostere Substitutions and Scaffold Hopping for Selective Control of Ostrinia furnacalis.

Chitin-degrading enzymes are critical components in regulating the molting process of the Asian corn borer and serve as potential targets for controlling this destructive pest of maize. Here, we used a scaffold-hopping strategy to design a series of efficient naphthylimide insecticides. Among them, compound 8c exhibited potent inhibition of chitinase from OfChi-h and OfChtI at low nanomolar concentrations (IC50 = 1.51 and 9.21 nM, respectively). Molecular docking simulations suggested that 8c binds to chitinase by mimicking the interaction of chitin oligosaccharide substrates with chitinase. At low ppm concentrations, compound 8c performed comparably to commercial insecticides in controlling the highly destructive plant pest, the Asian corn borer. Tests on a wide range of nontarget organisms indicate that compound 8c has very low toxicity. In addition, the effect of inhibitor treatment on the expression of genes associated with the Asian corn borer chitin-degrading enzymes was further investigated by quantitative real-time polymerase chain reaction. In conclusion, our study highlights the potential of 8c as a novel chitinase-targeting insecticide for effective control of the Asian corn borer, providing a promising solution in the quest for sustainable pest management.

Investigation of the Shared Biomarkers in Heterotopic Ossification Between Ossification of the Ligamentum Flavum and Ankylosing Spondylitis.

STUDY DESIGN: Bioinformatics analysis of Gene Expression Omnibus (GEO). OBJECTIVE: Ossification of the ligamentum flavum (OLF) and ankylosing spondylitis (AS) represent intricate conditions marked by the gradual progression of endochondral ossification. This investigation endeavors to unveil common biomarkers associated with heterotopic ossification and explore the potential molecular regulatory mechanisms. METHODS: Microarray and RNA-sequencing datasets retrieved from the Gene Expression Omnibus (GEO) repository were harnessed to discern differentially expressed genes (DEGs) within the OLF and AS datasets. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) was implemented to pinpoint co-expression modules linked to OLF and AS. Common genes were further subjected to an examination of functional pathway enrichment. Moreover, hub intersection genes were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by an evaluation of diagnostic performance in external OLF and AS cohorts. Lastly, an analysis of immune cell infiltration was conducted to scrutinize the correlation of immune cell presence with shared biomarkers in OLF and AS. RESULTS: A total of 1353 and 91 Differentially Expressed Genes (DEGs) were identified in OLF and AS, respectively. Using the Weighted Gene Co-expression Network Analysis (WGCNA), 2 modules were found to be notably significant for OLF and AS. The integrative bioinformatic analysis revealed 3 hub genes (MAB21L2, MEGF10, ISLR) as shared risk biomarkers, with MAB21L2 being the central focus. Receiver Operating Characteristic (ROC) analysis exhibited a strong diagnostic potential for these hub genes. Gene Ontology (GO) analysis indicated their involvement in the positive regulation of myoblast proliferation. Notably, MAB21L2 was singled out as the optimal common biomarker for OLF and AS. Furthermore, an analysis of immune infiltration demonstrated a correlation between MAB21L2 expression and changes in immune cells. Activated CD8 T cells were identified as shared differential immune infiltrating cells significantly linked to MAB21L2 in both OLF and AS. CONCLUSION: This study represents the first instance of identifying MAB21L2 as a prospective diagnostic marker for patients contending with OLF associated with AS. The research results indicate that the ECM-receptor interaction and the cell-cell adhesion may play a role in both disease processes. This newfound knowledge not only enhances our understanding of the pathogenesis behind spinal ligament ossification but also uncovers potential targets for therapeutic interventions.

Effect of Extended Care on Functional Rehabilitation of Stroke-Induced Hemiplegic Patients.

Background: We aimed to observe the effect of extended care on improving motor function and activities of daily living of stroke-induced hemiplegic patients. Methods: Patients clinically diagnosed as stroke with hemiplegia and hospitalized in the Neurology Department at Tianjin Haibin People's Hospital, China from 2019 to 2020 were selected. One hundred twenty patients were enrolled and randomly divided into the intervention group (60 patients) and the control group (60 patients). The control group was given routine rehabilitation treatment and care. Based on routine rehabilitation treatment and care, the intervention group was given transitional care. After discharge, the patients were followed up. Barthel indexes (BIs) were collected to evaluate the activities of daily living of patients. The Fugl-Meyer Motor Function Assessment (FMA) was adopted to evaluate the patients' motor function. Results: There was no statistically significant difference in the total BI scores between the two groups of patients at the two time points before intervention and at discharge. The total scores of the intervention group were higher than those of the control group after 1 month and 3 months of discharge, and the difference was statistically significant (P<0.05). There was no statistically significant difference in total FMA scores between the two groups of patients before intervention, indicating comparability. After 3 months of discharge, the total FMA score of the intervention group patients was higher than that of the control group, and the differences were statistically significant (P<0.05). Conclusion: Continuous care can effectively improve motor function and daily living ability of stroke patients with hemiplegia.

Development of Amorphous Solid Dispersion Sustained-Release Formulations with Polymer Composite Matrix-Regulated Stable Release Plateaus.

PURPOSE: This study was designed to develop ibuprofen (IBU) sustained-release amorphous solid dispersion (ASD) using polymer composites matrix with drug release plateaus for stable release and to further reveal intrinsic links between polymer' matrix ratios and drug release behaviors. METHODS: Hydrophilic polymers and hydrophobic polymers were combined to form different composite matrices in developing IBU ASD formulations by hot melt extrusion technique. The intrinsic links between the mixed polymer matrix ratio and drug dissolution behaviors was deeply clarified from the dissolution curves of hydrophilic polymers and swelling curves of composite matrices, and intermolecular forces among the components in ASDs. RESULTS: IBU + ammonio methacrylate copolymer type B (RSPO) + poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP VA64) physical mixtures presented unstable release behaviors with large error bars due to inhomogeneities at the micrometer level. However, IBU-RSPO-PVP VA64 ASDs showed a "dissolution plateau phenomenon", i.e., release behaviors of IBU in ASDs were unaffected by polymer ratios when PVP VA64 content was 35% ~ 50%, which could reduce risks of variations in release behaviors due to fluctuations in prescriptions/processes. The release of IBU in ASDs was simultaneously regulated by the PVP VA64-mediated "dissolution" and RSPO-PVP VA64 assembly-mediated "swelling". Radial distribution function suggested that similar intermolecular forces between RSPO and PVP VA64 were key mechanisms for the "dissolution plateau phenomenon" in ASDs at 35% ~ 50% of PVP VA64. CONCLUSIONS: This study provided ideas for developing ASD sustained-release formulations with stable release plateau modulated by polymer combinations, taking full advantages of simple process/prescription, ease of scale-up and favorable release behavior of ASD formulations.