The Different Concentrations of Applied Exogenous Sugars Widely Influence the Specificity, Significance and Physiological Relevance of Study Outcomings.

Plant growth and development are governed via signal networks that connect inputs from nutrient status, hormone signals, and environmental cues. Substantial researches have indicated a pivotal role of sugars as signalling molecules in plants that integrate external environmental cues and other nutrients with intrinsic developmental programmes regulated via multiple plant hormones. Therefore, plant growth and development are controlled through complication signalling networks. However, in many studies, to obtain more obviously experimental findings, excess concentrations of applied exogenous sugars have aggravated the complexity of this signalling networks. Once researchers underestimate this complexity, a series of contradictory or contrasting findings will be generated. More importantly, in terms of these contradictory findings, more contradictory study outcomings are derived. In this review, we carefully analyze some reports, and find that these reports have confused or neglected that the sugar-antagonism of ethylene signalling is specific or conditional. As a result, many contradictory conclusions are generated, which will in turn misdirect the scientific community.

Association between pets and dry eye symptoms: A Chinese national-based study.

BACKGROUND: Pet-derived allergens are another source of indoor air pollution which could affect human health. However, the association between pet ownership and the risk of dry eye symptoms (DES) remains to be elucidated. METHODS: We conducted a nationwide cross-sectional survey among Chinese residents aged over 12 years from June 20, 2022 to August 31, 2022. The Ocular Surface Disease Index-6 (OSDI-6) questionnaire was utilized to evaluate the presence of DES. Multivariable logistic regression models were used to analyze the associations between pet ownership and DES. Subgroup analyses were conducted based on sex, age, residence and affective disorders, and sensitivity analysis by excluding participants with major ocular diseases. The interactions between pet ownership and other risk factors on DES were explored in the additive scale by calculating the synergy index (SI). RESULTS: A total of 21,916 subjects replied to the questionnaire. The prevalence of DES was 43.6 % (95 % confidence interval (CI), 43.0 %-44.3 %). Pet ownership was significantly associated with increased risk of DES (Odds ratio (OR): 1.13, 95%CI: 1.05-1.21), especially among the elderly (OR: 1.28, 95%CI: 1.09-1.51) and urban residents (OR: 1.13, 95%CI: 1.04-1.24). The individual effect of allergic rhinitis on DES was 2.59 (95%CI: 1.27-5.53), while the joint effect of pets and allergic rhinitis was 5.26 (95%CI: 1.20-36.74), suggesting a synergistic interaction with a SI of 2.48 (95%CI: 0.25-24.39). Furthermore, the interaction analysis also indicated a synergistic interaction between pet ownership and low health literacy with a SI of 1.12 (95%CI: 0.66-1.87). CONCLUSION: Pet ownership was identified as a risk factor for DES. The synergistic interaction of pet ownership and allergic rhinitis suggests shared mechanisms between DES and allergic conditions.

Thermal Ablation of Pulmonary Nodules by Electromagnetic Navigation Bronchoscopy Combined With Real-Time CT-Based 3D Fusion Navigation:Report of One Case.

A nodule in the right middle lobe of the lung was treated by a combination of cone-beam CT,three-dimensional registration for fusion imaging,and electromagnetic navigation bronchoscopy-guided thermal ablation.The procedure lasted for 90 min,with no significant bleeding observed under the bronchoscope.The total radiation dose during the operation was 384 mGy.The patient recovered well postoperatively,with only a small amount of blood in the sputum and no pneumothorax or other complications.A follow-up chest CT on the first day post operation showed that the ablation area completely covered the lesion,and the patient was discharged successfully.

Coral-like AgNPs hybrided MOFs modulated with biopolymer polydopamine for synergistic antibacterial effect and biofilm eradication.

Bacterial contamination is an intractable challenge in food safety, environments and biomedicine fields, and places a heavy burden on society. Polydopamine (PDA), a high molecular biopolymer, is considered as a promising candidate to participate in the design of novel antibacterial agents with unique contributions in biocompatibility, adherence, photothermal and metal coordination ability. In this study, coral-like ZIFL-PDA@AgNPs with excellent antibacterial properties and biocompatibility were prepared by embedding AgNPs into the biopolymer PDA-modulated ZIFL-PDA nanostructures by green reduction method to solve the problem of poor stability of AgNPs. Based on the plasma resonance effect of AgNPs, coral-like ZIFL-PDA@AgNPs had enhanced photothermal properties compared with ZIFL-PDA. Due to the synergistic effect between antibacterial metal ions mainly Ag+ and the photothermal effect, coral-like ZIFL-PDA@AgNPs showed enhanced anti-mature biofilm and antibacterial properties, which was dependent on its concentration and sterilization time. In addition, regulated by the ZIFL-PDA nanostructure, coral-like ZIFL-PDA@AgNPs demonstrated a unique Ag+ long-time sustained release behavior, giving it an extended antibacterial validity period and good biocompatibility. Antibacterial mechanism experiments indicated that coral-like ZIFL-PDA@AgNPs can significantly damage the integrity of bacterial cell membrane, reduce the content of ATP in bacterial by affecting the activity of succinate dehydrogenase, and induce the accumulation of reactive oxygen species, ultimately leading to bacterial death.

Vapor Nucleation on Hybrid-Wetting Nanoconvex Surfaces: The Competition between Intrinsic Wettability and Topography.

Hybrid-wetting surfaces with hydrophilic spots reduced from the micrometer to nanometer scale have been confirmed to enhance vapor nucleation while simultaneously minimizing droplet pinning. Given that surface topography also plays a critical role in influencing nucleation characteristics, the effect of competition between intrinsic wettability and topography on nucleation remains unclear when both surface topography and hydrophilic regions approach the critical nucleation size. This work investigated vapor nucleation on two types of hybrid-wetting nanoconvex surfaces. On random hybrid-wetting convex surfaces, the most negative potential energy sites were located at the sides of the convex structures, leading vapor to preferentially nucleate at these locations, consistent with observations on homogeneous surfaces. Despite similar average potential energy values across the surface, wettability variations in hydrophilic and hydrophobic atoms significantly alter the surface energy distribution. As the wettability difference between hydrophilic and hydrophobic atoms increases, stronger hydrophilic atoms generate relatively higher local energy regions, promoting vapor rapid nucleation. The edge effect still exists at a hydrophilic atom ratio of 10%, and competition among hydrophilic spots impedes vapor nucleation and growth. However, when the ratio increases to 40%, the increased surface average potential energy promotes the probability of vapor contacting the surface, leading to rapid vapor nucleation on the sides of the convex structures. In addition, surface potential energy analysis and the Monte Carlo method revealed that nucleation locations on nanoconvex surfaces are governed by the competition between intrinsic wettability and topography. When the magnitude of the potential energy generated by the hydrophilic atoms exceeds that from the topography, stronger solid-liquid interactions at the top of the convex structure increase the likelihood of vapor contacting the surface, resulting in nucleation at the top. Conversely, when the magnitude of the potential energy generated by hydrophilic atoms is lower than that from topography, nucleation preferentially still occurs on the sides.

LIG1 is a novel marker for bladder cancer prognosis: evidence based on experimental studies, machine learning and single-cell sequencing.

Background: Bladder cancer, a highly fatal disease, poses a significant threat to patients. Positioned at 19q13.2-13.3, LIG1, one of the four DNA ligases in mammalian cells, is frequently deleted in tumour cells of diverse origins. Despite this, the precise involvement of LIG1 in BLCA remains elusive. This pioneering investigation delves into the uncharted territory of LIG1's impact on BLCA. Our primary objective is to elucidate the intricate interplay between LIG1 and BLCA, alongside exploring its correlation with various clinicopathological factors. Methods: We retrieved gene expression data of para-carcinoma tissues and bladder cancer (BLCA) from the GEO repository. Single-cell sequencing data were processed using the "Seurat" package. Differential expression analysis was then performed with the "Limma" package. The construction of scale-free gene co-expression networks was achieved using the "WGCNA" package. Subsequently, a Venn diagram was utilized to extract genes from the positively correlated modules identified by WGCNA and intersect them with differentially expressed genes (DEGs), isolating the overlapping genes. The "STRINGdb" package was employed to establish the protein-protein interaction (PPI) network.Hub genes were identified through the PPI network using the Betweenness Centrality (BC) algorithm. We conducted KEGG and GO enrichment analyses to uncover the regulatory mechanisms and biological functions associated with the hub genes. A machine-learning diagnostic model was established using the R package "mlr3verse." Mutation profiles between the LIG1^high and LIG1^low groups were visualized using the BEST website. Survival analyses within the LIG1^high and LIG1^low groups were performed using the BEST website and the GENT2 website. Finally, a series of functional experiments were executed to validate the functional role of LIG1 in BLCA. Results: Our investigation revealed an upregulation of LIG1 in BLCA specimens, with heightened LIG1 levels correlating with unfavorable overall survival outcomes. Functional enrichment analysis of hub genes, as evidenced by GO and KEGG enrichment analyses, highlighted LIG1's involvement in critical function such as the DNA replication, cellular senescence, cell cycle and the p53 signalling pathway. Notably, the mutational landscape of BLCA varied significantly between LIG1high and LIG1low groups.Immune infiltrating analyses suggested a pivotal role for LIG1 in immune cell recruitment and immune regulation within the BLCA microenvironment, thereby impacting prognosis. Subsequent experimental validations further underscored the significance of LIG1 in BLCA pathogenesis, consolidating its functional relevance in BLCA samples. Conclusions: Our research demonstrates that LIG1 plays a crucial role in promoting bladder cancer malignant progression by heightening proliferation, invasion, EMT, and other key functions, thereby serving as a potential risk biomarker.

Pan-Cancer Screening and Validation of CALU's Role in EMT Regulation and Tumor Microenvironment in Triple-Negative Breast Cancer.

Purpose: Cancer-associated fibroblasts (CAFs) significantly contribute to tumor progression and the development of resistance to therapies across a range of malignancies, notably breast cancer. This study aims to elucidate the specific role and prognostic relevance of CALU across multiple cancer types. Patients and Methods: The association between CALU expression and prognosis, along with clinical characteristics in BRCA, HNSC, KIRP, LGG, and LIHC, was analyzed using data from the TCGA, GTEx, and GEO databases. Transcriptomic analysis of TCGA BRCA project data provided insights into the interaction between CALU and epithelial-mesenchymal transition (EMT) marker genes. Using TIMER and TISCH databases, the correlation between CALU expression and tumor microenvironment infiltration was assessed, alongside an evaluation of CALU expression across various cell types. Furthermore, CALU's influence on TNBC BRCA cell lines was explored, and its expression in tumor tissues was confirmed through immunohistochemical analysis of clinical samples. Results: This study revealed a consistent upregulation of CALU across several tumor types, including BRCA, KIRP, LIHC, HNSC, and LGG, with elevated CALU expression being associated with unfavorable prognoses. CALU expression was particularly enhanced in clinical contexts linked to poor outcomes. Genomic analysis identified copy number alterations as the principal factor driving CALU overexpression. Additionally, a positive correlation between CALU expression and CAF infiltration was observed, along with its involvement in the EMT process in both CAFs and malignant cells. In vitro experiments demonstrated that CALU is highly expressed in TNBC-BRCA cell lines, and knockdown of CALU effectively reversed EMT progression and inhibited cellular migration. Immunohistochemical analysis of clinical samples corroborated the elevated expression of CALU in tumors, along with alterations in EMT markers. Conclusion: This comprehensive pan-cancer analysis underscores CALU's critical role in modulating the tumor microenvironment and facilitating cell migration via the EMT pathway, identifying it as a potential therapeutic target.

Quantum-secured LiDAR with Gaussian modulated coherent states.

LiDAR systems that rely on classical signals are susceptible to intercept-and-recent spoofing attacks, where a target attempts to avoid detection. To address this vulnerability, we propose a quantum-secured LiDAR protocol that utilizes Gaussian modulated coherent states for both range determination and spoofing attack detection. By leveraging the Gaussian nature of the signals, the LiDAR system can accurately determine the range of the target through cross-correlation analysis. Additionally, by estimating the excess noise of the LiDAR system, the spoofing attack performed by the target can be detected, as it can introduce additional noise to the signals. We have developed a model for target ranging and security check, and conducted numerical simulations to evaluate the Receiver Operating Characteristic (ROC) of the LiDAR system. The results indicate that an intercept-and-recent spoofing attack can be detected with a high probability at a low false-alarm rate. Furthermore, the proposed method can be implemented using currently available technology, highlighting its feasibility and practicality in real-world applications.

Taste Disturbance After Endoscopic Tympanoplasty with Tragal Cartilage Graft and Improvement Strategies.

Objectives: To explore the risk factors of early postoperative taste disturbance (EPTD) after type I endoscopic tympanoplasty and operative modification strategies to improve taste disturbance. Methods: This was a controlled study. One hundred and twenty-four patients who underwent type I endoscopic tympanoplasty with tragal cartilage graft were separated evenly into control and modified groups. The full-thickness tragus cartilage graft was placed close to the bony annulus to ensure drum integrity in the control group, and in the modified group, the cartilage graft was not in contact with the posterior-superior bony annulus, and the inferior-posterior of the scutum. Univariate and multivariate models were used to analyze the possible factors affecting EPTD and the prognosis of taste recovery. Results: The incidence of EPTD was significantly lower in the modification group (24.19%) than in the control group (56.45%) (OR: 4.24, 95% CI: 1.93-9.33, P < .001). Surgical manipulation of the chorda tympani nerve resulted in a higher incidence of EPTD (OR: 2.43; 95% CI: 1.06-5.57, P = .035). The size of the graft did not affect taste disturbance. No difference in the taste recovery rate was observed between the control and test groups (Z = -1.57, P = .116) after 3 months. The recovery rate of patients with manipulated chorda tympani nerves was still lower than that of patients without at 3 months (Z = -2.74, P = .006). Conclusion: Modified surgery and reduced manipulation of the chorda tympani nerve effectively reduce EPTD. Manipulated chorda tympani nerves may have a persistent effect on taste recovery.

A Systematic Methodology for the Identification of the Chemical Composition of the Mongolian Drug Erdun-Uril Compound Utilizing UHPLC-Q-Exactive Orbitrap Mass Spectrometry.

The traditional Mongolian medicine Erdun-Uril is a conventional combination of 29 herbs commonly used for the treatment of cerebrovascular ailments. It has the effects of reducing inflammation, counteracting oxidative stress, and averting strokes caused by persistent cerebral hypoperfusion. Prior research on Erdun-Uril has predominantly concentrated on its pharmacodynamics and mechanism of action; however, there has been a lack of systematic and comprehensive investigation into its chemical constituents. Therefore, it is crucial to establish an efficient and rapid method for evaluating the chemical constituents of Erdun-Uril. In this study, Erdun-Uril was investigated using UHPLC-Q-Exactive Orbitrap MS combined with parallel reaction monitoring for the first time. Eventually, a total of 237 compounds, including 76 flavonoids, 68 phenolic compounds, 19 alkaloids, 7 amino acids, etc., were identified based on the chromatographic retention time, bibliography data, MS/MS2 information, neutral loss fragments (NLFs), and diagnostic fragment ions (DFIs). And of these, 225 were reported for the first time in this study. This new discovery of these complex components would provide a reliable theoretical basis for the development of pharmacodynamics and quality standards of the Mongolian medicine Erdun-Uril.

Liraglutide ameliorates diabetic kidney disease by modulating gut microbiota and L-5-Oxoproline.

The gut microbiome-metabolites-kidney axis is a potential target for treating diabetic kidney disease (DKD). Our previous study found that Liraglutide attenuated DKD in rats by decreasing renal tubular ectopic lipid deposition (ELD) and serum metabolites levels, including L-5-Oxoproline (5-OP). However, the response of gut microbiome-metabolites-kidney axis to Liraglutide in DKD rats and the effect of 5-OP on ELD remain unknown. In this study, Sprague-Dawley rats were used as an animal model of DKD. They were subjected to a high fat diet, streptozotocin and uninephrectomy, followed by Liraglutide treatment (0.4 mg/kg d). Additionally, HK-2 cells were incubated with 30 mM glucose and 200 µM palmitate for 24h, and exposed to different concentrations of 5-OP. In DKD rats, Liraglutide dramatically improved the renal tubule structure. It increased the Simpson index (F = 4.487, p = 0.035) and reduced the Actinobacteria-to-Bacteroidetes ratio (F = 6.189, p = 0.014). At the genus level, Liraglutide increased the relative abundance of Clostridium, Oscillospira, Sarcina, SMB53, and 02d06 while decreasing that of Allobaculum. Meanwhile, 13 metabolites were significantly altered after Liraglutide treatment. Multi-omics analysis found that 5-OP levels were positively correlated with Clostridium abundance but negatively correlated with renal injury related indicators. In HK-2 cells, 5-OP significantly reduced the ELD in a dose-dependent manner through inhibiting the expression of SREBP1 and FAS. Overall, the renoprotective effect of Liraglutide in DKD rats is linked to the improvement of the gut microbiota composition and increased serum 5-OP levels, which may reduce ELD in renal tubular cells by lowering lipid synthesis.

The interplay between metal ions and immune cells in glioma: pathways to immune escape.

This review explores the intricate roles of metal ions-iron, copper, zinc, and selenium-in glioma pathogenesis and immune evasion. Dysregulated metal ion metabolism significantly contributes to glioma progression by inducing oxidative stress, promoting angiogenesis, and modulating immune cell functions. Iron accumulation enhances oxidative DNA damage, copper activates hypoxia-inducible factors to stimulate angiogenesis, zinc influences cell proliferation and apoptosis, and selenium modulates the tumor microenvironment through its antioxidant properties. These metal ions also facilitate immune escape by upregulating immune checkpoints and secreting immunosuppressive cytokines. Targeting metal ion pathways with therapeutic strategies such as chelating agents and metalloproteinase inhibitors, particularly in combination with conventional treatments like chemotherapy and immunotherapy, shows promise in improving treatment efficacy and overcoming resistance. Future research should leverage advanced bioinformatics and integrative methodologies to deepen the understanding of metal ion-immune interactions, ultimately identifying novel biomarkers and therapeutic targets to enhance glioma management and patient outcomes.

Prediction of mutation-induced protein stability changes based on the geometric representations learned by a self-supervised method.

BACKGROUND: Thermostability is a fundamental property of proteins to maintain their biological functions. Predicting protein stability changes upon mutation is important for our understanding protein structure-function relationship, and is also of great interest in protein engineering and pharmaceutical design. RESULTS: Here we present mutDDG-SSM, a deep learning-based framework that uses the geometric representations encoded in protein structure to predict the mutation-induced protein stability changes. mutDDG-SSM consists of two parts: a graph attention network-based protein structural feature extractor that is trained with a self-supervised learning scheme using large-scale high-resolution protein structures, and an eXtreme Gradient Boosting model-based stability change predictor with an advantage of alleviating overfitting problem. The performance of mutDDG-SSM was tested on several widely-used independent datasets. Then, myoglobin and p53 were used as case studies to illustrate the effectiveness of the model in predicting protein stability changes upon mutations. Our results show that mutDDG-SSM achieved high performance in estimating the effects of mutations on protein stability. In addition, mutDDG-SSM exhibited good unbiasedness, where the prediction accuracy on the inverse mutations is as well as that on the direct mutations. CONCLUSION: Meaningful features can be extracted from our pre-trained model to build downstream tasks and our model may serve as a valuable tool for protein engineering and drug design.

Seawater barium and sulfide removal improved marine habitability for the Cambrian Explosion of early animals.

An increase in atmospheric pO2 has been proposed as a trigger for the Cambrian Explosion at ∼539-514 Ma but the mechanistic linkage remains unclear. To gain insights into marine habitability for the Cambrian Explosion, we analysed excess Ba contents (Baexcess) and isotope compositions (δ138Baexcess) of ∼521-Myr-old metalliferous black shales in South China. The δ138Baexcess values vary within a large range and show a negative logarithmic correlation with Baexcess, suggesting a major (>99%) drawdown of oceanic Ba inventory via barite precipitation. Spatial variations in Baexcess and δ138Baexcess indicate that Ba removal was driven by sulfate availability that was ultimately derived from the upwelling of deep seawaters. Global oceanic oxygenation across the Ediacaran-Cambrian transition may have increased the sulfate reservoir via oxidation of sulfide and concurrently decreased the Ba reservoir by barite precipitation. The removal of both H2S and Ba that are deleterious to animals could have improved marine habitability for early animals.

[Perioperative nursing for patients undergoing autologous dermis grafting for penile girth augmentation and penile lengthening].

OBJECTIVE: To explore the perioperative nursing methods of autologous dermal transplantation for penile girth enhancement combined with penile lengthening surgery. METHODS: Summarize the perioperative nursing data of 5 patients with small penis who underwent autologous groin dermal transplantation for penile girth enhancement combined with penile lengthening surgery. RESULTS: After comprehensive perioperative nursing, all 5 patients recovered well after the surgery. The preoperative APPSSI scores of the patients were 4.60±0.48, which were all less than 6 points. The postoperative APPSSI scores at 2 months, 6 months, and 12 months were 9－12 (10.6±1.02), 10－12 (11.2±0.98), and 10－12 (11.2±0.98) respectively, showing satisfaction with the surgical outcomes. There was a statistically significant difference compared to the preoperative APPSSI scores (ï¼°<0.05). The preoperative SAS scores were 45－58 (52.2±4.35), and the SAS scores at 2 months, 6 months, and 12 months postoperatively were 31－40 (34.2±3.31), 30-41 (35.8±3.65), and 33－40 (35.6±2.33) respectively, indicating a reduction in anxiety levels after the surgery, with a statistically significant difference compared to the preoperative SAS scores (P<0.05). The preoperative IIEF-5 scores were 7－15 (10.4±2.87), and the IIEF-5 scores at 2 months, 6 months, and 1 year postoperatively were 16－24 (19.8±2.71), 18－25 (21.2±2.48), and 18－24 (20.8±2.39) respectively, showing a significant improvement postoperatively, with statistical significance (P<0.05). The preoperative NPTR examination showed a sustained erection time of 18－25 (21.2±2.59) minutes, and the NPTR examination at 2 months, 6 months, and 1 year postoperatively showed sustained erection times of 18－24 (21.8±2.28), 20-25 (23.4±2.30), and 24－27 (25.4±1.14) minutes respectively. There was no statistically significant difference in the sustained erection time at 2 months and 6 months postoperatively compared to preoperative NPTR examination, but there was a statistically significant difference at 12 months postoperatively (P<0.01). CONCLUSION: Comprehensive perioperative nursing is an important factor in achieving high satisfaction with the surgery, promoting postoperative recovery, and improving the quality of sexual life for patients undergoing autologous groin dermal transplantation for penile girth enhancement combined with penile lengthening surgery.

[Effect of Sakuranetin on Microglia-Mediated Neuroinflammation After Spinal Cord Injury].

Objective To investigate the effects of sakuranetin (SK) on motor functions in the mouse model of spinal cord injury (SCI) and decipher the mechanism.Methods Fifty-four C57BL/6J mice were randomized into sham,SCI,and SK groups.The mice in the sham group underwent only laminectomy at T9,while those in the SCI and SK groups were subjected to spinal cord contusion injury at T9.Behavioral tests were conducted at different time points after surgery to evaluate the motor functions of mice in each group.The pathological changes in the tissue were observed to assess the extent of SCI in each group.The role and mechanism of SK in SCI were predicted by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses.Reverse transcription real-time fluorescence quantitative PCR,ELISA,and immunofluorescence were employed to evaluate the inflammation and activation of microglia in SCI mice.BV2 cells in vitro were classified into control (Con),lipopolysaccharide (LPS),and LPS+SK groups.The effects of SK intervention on the release of inflammatory cytokines and the activation of BV2 cells were evaluated.Furthermore,the phosphatidylinositol-3-kinase(PI3K)/protein kinase B (AKT) signaling pathway activator insulin-like growth factor-1 (IGF-1) was used to treat the SK-induced BV2 cells in vitro (SK+IGF-1 group),and SK was used to treat the IGF-1-induced BV2 cells in vitro (IGF-1+SK group).Western blotting was conducted for molecular mechanism validation.Results Behavioral tests and histological staining results showed that compared with the SCI group,the SK group exhibited improved motor abilities and reduced area of damage in the spinal cord tissue (all P<0.001).The GO enrichment analysis predicted that SK may be involved in the inflammation following SCI.The KEGG enrichment analysis predicted that SK regulated the PI3K/Akt pathway to exert the neuroprotective effect.The results from in vitro and in vivo experiments showed that SK lowered the levels of tumor necrosis factor-α,interleukin-6,and interleukin-1ß and inhibited the activation of microglia (all P<0.05).The results of Western blotting showed that SK down-regulated the phosphorylation levels of PI3K and Akt (all P<0.001) and inhibited the IGF-1-induced elevation of PI3K and Akt phosphorylation levels (all P<0.001).Conversely,IGF-1 had the opposite effects (P=0.001,P<0.001).The results of reverse transcription real-time fluorescence quantitative PCR,ELISA,and immunofluorescence showed that the SK+IGF-1 group had higher levels of inflammatory cytokines and more activated microglia than the SK group(all P<0.05).Conclusion SK may suppress the activation of the PI3K/Akt pathway to inhibit the inflammation mediated by SCI-induced activation of microglia,ameliorate the pathological damage of the spinal cord tissue,and promote the recovery of motor functions in SCI mice.

Disulfide-stabilized trimeric hemagglutinin ectodomains provide enhanced heterologous influenza protection.

Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund's adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.

Pathologic Status of Tissue Around the Malleus Handle Tip in Endoscopic Tympanoplasty: Potential Impact on Surgical Decisions.

Objectives: To avoid postoperatively acquired cholesteatoma, whether there was any squamous epithelial tissues residue around the tip of the malleus handle, and the need to remove these tissues were explored. Methods: This prospective study enrolled 197 patients who underwent endoscopic tympanoplasty. A postoperative pathological evaluation of the tissue around the tip of the malleus handle was performed to determine the presence of squamous epithelium. Analyzed correlation of epithelial remnants with exposure of malleus handle and microbial infection of middle ear. Results: The detection rate of squamous epithelial retention around the tip of the malleus handle differed significantly among patients with adhesive otitis media (AdOM), acquired cholesteatoma, and chronic suppurative otitis media (CSOM). The detection rate was significantly higher in the acquired cholesteatoma group than in the AdOM and CSOM groups (P < .001). The rate of squamous epithelial retention around the tip of the malleus handle was not significantly associated with microbial infection of the middle ear, the surgical side (P = .672), dry or wet ear status (P = .702), or exposure of the malleus handle (P = .06). Conclusions: In patients with acquired cholesteatoma, AdOM, or COM with severe tympanic sclerosis, the tissue around the tip of the malleus handle should be removed completely. For patients with simple COM, that is, without tympanic sclerosis or keratinizing stratified squamous epithelium at the edge of the perforation, the tissue can be retained.

Exploring drug repositioning possibilities of kinase inhibitors via molecular simulation.

Kinases, a class of enzymes controlling various substrates phosphorylation, are pivotal in both physiological and pathological processes. Although their conserved ATP binding pockets pose challenges for achieving selectivity, this feature offers opportunities for drug repositioning of kinase inhibitors (KIs). This study presents a cost-effective in silico prediction of KIs drug repositioning via analyzing cross-docking results. We established the KIs database (278 unique KIs, 1834 bioactivity data points) and kinases database (357 kinase structures categorized by the DFG motif) for carrying out cross-docking. Comparative analysis of the docking scores and reported experimental bioactivity revealed that the Atypical, TK, and TKL superfamilies are suitable for drug repositioning. Among these kinase superfamilies, Olverematinib, Lapatinib, and Abemaciclib displayed enzymatic activity in our focused AKT-PI3K-mTOR pathway with IC50 values of 3.3, 3.2 and 5.8 µM. Further cell assays showed IC50 values of 0.2, 1.2 and 0.6 µM in tumor cells. The consistent result between prediction and validation demonstrated that repositioning KIs via in silico method is feasible.

Metal-Organic Framework-Based Photodetectors.

The unique and interesting physical and chemical properties of metal-organic framework (MOF) materials have recently attracted extensive attention in a new generation of photoelectric applications. In this review, we summarized and discussed the research progress on MOF-based photodetectors. The methods of preparing MOF-based photodetectors and various types of MOF single crystals and thin film as well as MOF composites are introduced in details. Additionally, the photodetectors applications for X-ray, ultraviolet and infrared light, biological detectors, and circularly polarized light photodetectors are discussed. Furthermore, summaries and challenges are provided for this important research field.