Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer invasiveness by activation of target of rapamycin kinase/autophagy signaling.

BACKGROUND: Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers. AIM: To investigate the role of MOB3B in colorectal cancer (CRC). METHODS: This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results. RESULTS: MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts. CONCLUSION: Loss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.

Microbiome-host interactions in the pathogenesis of acute exacerbation of chronic obstructive pulmonary disease.

Objective: To explore the underlying mechanisms the airway microbiome contributes to Acute Exacerbation of Chronic Obstructive Pulmonary Disease(AECOPD). Methods: We enrolled 31 AECOPD patients and 26 stable COPD patients, their sputum samples were collected for metagenomic and RNA sequencing, and then subjected to bioinformatic analyses. The expression of host genes was validated by Quantitative Real-time PCR(qPCR) using the same batch of specimens. Results: Our results indicated a higher expression of Rothia mucilaginosa(p=0.015) in the AECOPD group and Haemophilus influenzae(p=0.005) in the COPD group. The Different expressed genes(DEGs) detected were significantly enriched in "type I interferon signaling pathway"(p<0.001, q=0.001) in gene function annotation, and "Cytosolic DNA-sensing pathway"(p=0.002, q=0.024), "Toll-like receptor signaling pathway"(p=0.006, q=0.045), and "TNF signaling pathway"(p=0.006, q=0.045) in KEGG enrichment analysis. qPCR amplification experiment verified that the expression of OASL and IL6 increased significantly in the AECOPD group. Conclusion: Pulmonary bacteria dysbiosis may regulate the pathogenesis of AECOPD through innate immune system pathways like type I interferon signaling pathway and Toll-like receptor signaling pathway.

The Bursaphelenchus xylophilus Effector BxNMP1 Targets PtTLP-L2 to Mediate PtGLU Promoting Parasitism and Virulence in Pinus thunbergii.

Pinus is an important economic tree species, but pine wilt disease (PWD) seriously threatens the survival of pine trees. PWD caused by Bursaphelenchus xylophilus is a major quarantine disease worldwide that causes significant economic losses. However, more information about its molecular pathogenesis is needed, resulting in a lack of effective prevention and treatment measures. In recent years, effectors have become a hot topic in exploring the molecular pathogenic mechanism of pathogens. Here, we identified a specific effector, BxNMP1, from B. xylophilus. In situ hybridization experiments revealed that BxNMP1 was specifically expressed in dorsal gland cells and intestinal cells, and RT-qPCR experiments revealed that BxNMP1 was upregulated in the early stage of infection. The sequence of BxNMP1 was different in the avirulent strain, and when BxNMP1-silenced B. xylophilus was inoculated into P. thunbergii seedlings, the disease severity significantly decreased. We demonstrated that BxNMP1 interacted with the thaumatin-like protein PtTLP-L2 in P. thunbergii. Additionally, we found that the ß-1,3-glucanase PtGLU interacted with PtTLP-L2. Therefore, we hypothesized that BxNMP1 might indirectly interact with PtGLU through PtTLP-L2 as an intermediate mediator. Both targets can respond to infection, and PtTLP-L2 can enhance the resistance of pine trees. Moreover, we detected increased salicylic acid contents in P. thunbergii seedlings inoculated with B. xylophilus when BxNMP1 was silenced or when the PtTLP-L2 recombinant protein was added. In summary, we identified a key virulence effector of PWNs, BxNMP1. It positively regulates the pathogenicity of B. xylophilus and interacts directly with PtTLP-L2 and indirectly with PtGLU. It also inhibits the expression of two targets and the host salicylic acid pathway. This study provides theoretical guidance and a practical basis for controlling PWD and breeding for disease resistance.

Piezoelectric Active Sensing-Based Pipeline Corrosion Monitoring Using Singular Spectrum Analysis.

Pipelines are an important transportation form in industry. However, pipeline corrosion, particularly that occurring internally, poses a significant threat to safe operations. To detect the internal corrosion of a pipeline, a method utilizing piezoelectric sensors alongside singular spectrum analysis is proposed. Two piezoelectric patches are affixed to the exterior surface of the pipeline, serving the roles of an actuator and a sensor, respectively. During the detection, the signals excited by the actuator are transmitted through the pipeline's wall and are received by PZT2 through different paths, and the corresponding piezoelectric sensor captures the signals. Then, the response signals are denoised by singular spectrum analysis, and the first several wave packets in the response signals are selected to establish a feature for pipeline corrosion detection. At last, the envelope area of the selected packets is calculated as a feature to detect corrosion. To validate the proposed method, corrosion monitoring experiments are performed. The experimental results indicate that the envelope area of the first several wave packets from the response signals, following singular spectrum analysis, can serve as a feature to assess the degree of pipeline corrosion, and the index has a monotonic relationship with the corrosion depth of the pipeline. This method provides an effective way for pipeline corrosion monitoring.

Development and Application of Cationic Nile Blue Probes in Live-Cell Super-Resolution Imaging and Specific Targeting to Mitochondria.

Mitochondria are essential organelles involved in various metabolic processes in eukaryotes. The imaging, targeting, and investigation of cell death mechanisms related to mitochondria have garnered significant interest. Small-molecule fluorescent probes have proven to be robust tools for utilizing light to advance the study of mitochondrial biology. In this study, we present the rational design of cationic Nile blue probes carrying a permanent positive charge for these purposes. The cationic Nile blue probes exhibit excellent mitochondrial permeability, unique solvatochromism, and resistance to oxidation. We observed weaker fluorescence in aqueous solutions compared to lipophilic solvents, thereby minimizing background fluorescence in the cytoplasm. Additionally, we achieved photoredox switching of the cationic Nile blue probes under mild conditions. This enabled us to demonstrate their application for the first time in single-molecule localization microscopy of mitochondria, allowing us to observe mitochondrial fission and fusion behaviors. Compared to conventional cyanine fluorophores, this class of dyes demonstrated prolonged resistance to photobleaching, likely due to their antioxidation properties. Furthermore, we extended the application of cationic Nile blue probes to the mitochondria-specific delivery of taxanes, facilitating the study of direct interactions between the drug and organelles. Our approach to triggering cell death without reliance on microtubule binding provides valuable insights into anticancer drug research and drug-resistance mechanisms.

Enantioselective Reductive Cyclization of Alkynyl-Tethered Cyclohexadienones Catalyzed by Rhodium Complexes.

Although various types of asymmetric cyclization reactions of 1,6-enynes have been established, simple asymmetric reductive cyclization remains underdeveloped. In this study, the enantioselective reductive cyclization of alkynyl-tethered cyclohexadienones (1,6-enynes) has been developed via a chiral pincer rhodium catalyst, affording cis-hydrobenzofurans and cis-hydroindoles with high enantioselectivities (90-99% ee). Furthermore, several synthetic applications and preliminary inhibitory activity studies against SARS-CoV-2 3CLpro are presented.

High bioavailable testosterone levels increase the incidence of isolated REM sleep behavior disorder: Results from multivariable and network Mendelian randomization analysis.

OBJECTIVES: To explore the causal relationships between sex hormone levels and incidence of isolated REM sleep behavior disorder (iRBD). METHODS: In our study, we utilized Genome-Wide Association Studies (GWAS) data for iRBD, including 9447 samples with 1061 cases of iRBD provided by the International RBD Study Group. Initially, we conducted a two-sample univariate MR analysis to explore the impact of sex hormone-related indicators on iRBD. This was followed by the application of multivariable MR methods to adjust for other hormone levels and potential confounders. Finally, we undertook a network MR analysis, employing brain structure Magnetic Resonance Imaging (MRI) characteristics as potential mediators, to examine whether sex hormones could indirectly influence the incidence of iRBD by affecting brain structure. RESULTS: Bioavailable testosterone (BioT) is an independent risk factor for iRBD (Odds Ratio [95 % Confidence Interval] = 2.437 [1.308, 4.539], P = 0.005, corrected-P = 0.020), a finding that remained consistent even after adjusting for other sex hormone levels and potential confounders. Additionally, BioT appears to indirectly increase the risk of iRBD by reducing axial diffusivity and increasing the orientation dispersion index in the left cingulum and cingulate gyrus. CONCLUSIONS: Our research reveals that elevated levels of BioT contribute to the development of iRBD. However, the specific impact of BioT on different sexes remains unclear. Furthermore, high BioT may indirectly lead to iRBD by impairing normal pathways in the left cingulum and cingulate gyrus and fostering abnormal pathway formation.

Design and Verification of Piano Playing Assisted Hand Exoskeleton Robot.

Finger technique is a crucial aspect of piano learning, and hand exoskeleton mechanisms effectively assist novice piano players in maintaining correct finger technique consistently. Addressing current issues with exoskeleton robots, such as the inability to provide continuous correction of finger technique and their considerable weight, a novel hand exoskeleton robot has been developed to enhance finger technique through continuous correction and reduced weight. Initial data are gathered using finger joint angle sensors to analyze movements during piano playing, focusing on the trajectory and angular velocity of key strikes. This analysis informs the design of a 6-bar double-closed-loop mechanism with an end equivalent sliding pair, using analytical methods to establish the relationship between motor extension and input rod rotation. Simulation studies assess the exoskeleton's motion space and dynamics, confirming its capability to meet structural and functional demands for accurate key striking. Prototype testing validates the exoskeleton's ability to maintain correct finger positioning and mimic natural strike speeds, thus improving playing technique while ensuring comfort and safety.

A Study on the Design of Knee Exoskeleton Rehabilitation Based on the RFPBS Model.

The gait rehabilitation knee exoskeleton is an advanced rehabilitative assistive device designed to help patients with knee joint dysfunction regain normal gait through training and activity support. This paper introduces a design framework based on the process knowledge representation method to optimize the design and control efficiency of the knee exoskeleton. This framework integrates knowledge of design objects and processes, specifically including requirements, functions, principle work areas, and the representation and multi-dimensional dynamic mapping of the Behavior-Structure (RFPBS) matrix, achieving multi-dimensional dynamic mapping of the knee exoskeleton. This method incorporates biomechanical and physiological knowledge from the rehabilitation process to more effectively simulate and support gait movements during rehabilitation. Research results indicate that the knee rehabilitation exoskeleton design, based on the RFPBS process knowledge representation model, accomplishes multi-dimensional dynamic mapping, providing a scientific basis and effective support for the rehabilitation of patients with knee joint dysfunction.

Low frequency of repetitive trans-spinal magnetic stimulation promotes functional recovery after spinal cord injury in mice through inhibiting TGF-ß1/Smad2/3 signaling pathway.

Spinal cord injury (SCI) remains a worldwide challenge due to limited treatment strategies. Repetitive trans-spinal magnetic stimulation (rTSMS) is among the most cutting-edge treatments for SCI. However, the mechanism underlying rTSMS on functional recovery is still unclear. In this study, 8-week-old C57BL/6J female mice were used to design SCI models followed by treatment with monotherapy (1 Hz rTSMS or LY364947) or combination therapy (rTSMS + LY364947). Our results showed obvious functional recovery after monotherapies compared to untreated mice. Immunofluorescence results demonstrated that rTSMS and LY364947 modulate the lesion scar by decreasing fibrosis and GFAP and possess the effect on neural protection. In addition, rTSMS suppressed inflammation and the activation of TGFß1/Smad2/3 signaling pathway, as evidenced by markedly reduced TGF-ßRⅠ, Smad2/3, and p-Smad2/3 compared with untreated mice. Overall, it was confirmed that 1 Hz rTSMS promotes SCI recovery by suppressing the TGFß1/Smad2/3 signaling, revealing a novel pathological mechanism of 1 Hz rTSMS intervention, and may provide potential targets for clinical treatment.

Modular access to diarylmethyl sulfonamides via visible light-promoted cross-coupling reactions.

We report a novel and efficient method for the preparation of diarylmethyl sulfonamide derivatives through visible-light-induced sulfamoylation of para-quinone methides with sulfamoyl chlorides under mild, metal-free conditions. This protocol demonstrates excellent tolerance toward a wide range of functional groups, affording the corresponding products in moderate to high yields. Preliminary mechanism studies revealed that the excited photocatalyst rhodamine 6G* was mainly quenched by para-quinone methides and the generated diarylmethyl radical intermediates then underwent radical-radical cross-coupling with sulfamoyl radicals to yield the diarylmethyl sulfonamides.

Connectome gradient dysfunction contributes to white matter hyperintensity-related cognitive decline.

BACKGROUND: Although white matter hyperintensity (WMH) is closely associated with cognitive decline, the precise neurobiological mechanisms underlying this relationship are not fully elucidated. Connectome studies have identified a primary-to-transmodal gradient in functional brain networks that support the spectrum from sensation to cognition. However, whether connectome gradient structure is altered as WMH progresses and how this alteration is associated with WMH-related cognitive decline remain unknown. METHODS: A total of 758 WMH individuals completed cognitive assessment and resting-state functional MRI (rs-fMRI). The functional connectome gradient was reconstructed based on rs-fMRI by using a gradient decomposition framework. Interrelations among the spatial distribution of WMH, functional gradient measures, and specific cognitive domains were explored. RESULTS: As the WMH volume increased, the executive function (r = -0.135, p = 0.001) and information-processing speed (r = -0.224, p = 0.001) became poorer, the gradient range (r = -0.099, p = 0.006), and variance (r = -0.121, p < 0.001) of the primary-to-transmodal gradient reduced. A narrower gradient range (r = 0.131, p = 0.001) and a smaller gradient variance (r = 0.136, p = 0.001) corresponded to a poorer executive function. In particular, the relationship between the frontal/occipital WMH and executive function was partly mediated by gradient range/variance of the primary-to-transmodal gradient. CONCLUSIONS: These findings indicated that WMH volume, the primary-to-transmodal gradient, and cognition were interrelated. The detrimental effect of the frontal/occipital WMH on executive function was partly mediated by the decreased differentiation of the connectivity pattern between the primary and transmodal areas.

Response of soil particles around bedrock outcrops to sorting of rock surface flow derived outcrops in a rocky desertification area.

Soils around bedrock outcrops, even if they are protected by vegetation to some extent after ecological restoration, are prone to being washed away by rock surface flow (RSF) derived from these outcrops in rocky desertification land. However, the extent of the scouring scale and sorting effect of RSF on the soils around outcrops remains unknown. To solve this problem, a series of soils around bedrock outcrops exposed in sloping farmland (SF, without RSF), abandoned land (AL, 1 year of RSF) and shrub-grassland (SG, 5 years of RSF) were examined by the laser diffraction method in a natural ecological restoration area of rocky desertification, where the duration of the RSF is also the time for ecological restoration. It was found that the RSF had a limited effect on the particle size distribution of the soils, only having a significant scouring effect on the soils at the rock-soil interface within a horizontal distance of 2 cm from the outcrops and an insignificant effect on the soils far away from the outcrops in terms of horizontal distance (10 cm and 20 cm). The particle size distributions of the soil around the outcrops were related to erosion caused by the RSF, but mainly benefited from ecological restoration. Compared with SF, the fine particle content in the soils around the outcrops significantly decreased in AL, but significantly increased in SG. Within a short period (1 year) after natural recovery, the RSF had a reduced effect on the fine particles of the soil around the outcrops; however, this did not occur after a long period (5 years). The results of this study further explain the influence of the RSF on soil erosion and leakage loss in karst areas.

Cellular senescence in metastatic prostate cancer: A therapeutic opportunity or challenge (Review).

The treatment of patients with metastatic prostate cancer (PCa) is considered to be a long­standing challenge. Conventional treatments for metastatic PCa, such as radical prostatectomy, radiotherapy and androgen receptor­targeted therapy, induce senescence of PCa cells to a certain extent. While senescent cells can impede tumor growth through the restriction of cell proliferation and increasing immune clearance, the senescent microenvironment may concurrently stimulate the secretion of a senescence­associated secretory phenotype and diminish immune cell function, which promotes PCa recurrence and metastasis. Resistance to established therapies is the primary obstacle in treating metastatic PCa as it can lead to progression towards an incurable state of disease. Therefore, understanding the molecular mechanisms that underly the progression of PCa is crucial for the development of novel therapeutic approaches. The present study reviews the phenomenon of treatment­induced senescence in PCa, the dual role of senescence in PCa treatments and the mechanisms through which senescence promotes PCa metastasis. Furthermore, the present review discusses potential therapeutic strategies to target the aforementioned processes with the aim of providing insights into the evolving therapeutic landscape for the treatment of metastatic PCa.

Flow and performance: a quantitative study of elicitation modeling in a piano performance perspective.

Introduction: Flow, defined as a heightened state of consciousness characterized by intense concentration during an activity, is influenced primarily by the perceived challenge and the dynamic equilibrium of skills. This investigation focuses on the patterns of flow state attainment and its elicitation mechanisms within the context of piano performance among Chinese music college students. Methods: Our study establishes a framework for accessing flow, utilizing quantitative data from music ontology to gauge the level of challenge and the level of music acquisition to assess skills. Additionally, we integrate external factors such as music culture heterogeneity and demographic variables to elucidate the causes and moderating effects of flow on piano performance. Results: The findings reveal a positive correlation between flow and performance, with the model of challenge and skill induction partially explaining these results. Notably, melodic Shannon Entropy emerges as a potential indicator of challenge, suggesting its relevance in future studies on flow. Discussion: This research provides multidimensional insights into the interplay between performance and flow in piano performance, guiding future investigations to explore the musical quantitative perspective more deeply.

Protocol for differentiation of monocytes and macrophages from human induced pluripotent stem cells.

Study of disease-relevant immune cells, namely monocytes and macrophages, is limited based on availability of primary tissue, a limitation that can be remedied using human induced pluripotent stem cell (hiPSC) technology. Here, we present a protocol for differentiation of monocytes and macrophages from hiPSCs. We describe steps for hiPSC maintenance, mesoderm lineage induction, hematopoietic progenitor cells (HPCs) commitment and expansion, and myeloid lineage induction. We then detail procedures for monocyte formation and functional macrophage formation and polarization. For complete details on the use and execution of this protocol, please refer to Chen et al.1.

Metformin overcomes chemoresistance by regulating stemness via KLF4 in oral squamous cell carcinoma.

OBJECTIVE: Chemoresistance is a common event after chemotherapy, including oral squamous cell carcinoma (OSCC). Accumulated evidence suggests that the cancer stemness significantly contributes to therapy resistance. An unresolved question remains regarding how to effectively overcome OSCC chemoresistance by targeting stemness. This study aims to investigate the antitumor effect of metformin and clarify the potential molecular mechanisms. METHODS: Cellular models resistant to chemotherapy were established, and their viability and sphere-forming ability were assessed using CCK-8 and soft agar formation assays, respectively. RNA-seq and Western blotting analyses were employed to delve into the molecular pathways. Furthermore, to corroborate the inhibitory effects of metformin and cisplatin at an animal level, a subcutaneous tumor transplantation model was instituted. RESULTS: Metformin as a monotherapy exhibited inhibition of stemness traits via Krüppel-like factor 4 (KLF4). Metformin and cisplatin can synergically inhibit cell proliferation and induce cell apoptosis. Animal experiments confirmed the inhibitory effect of cisplatin and metformin on tumor in mice. CONCLUSION: Our study proposes a potential therapeutic approach of combining chemotherapy with metformin to overcome chemoresistance in OSCC.

Mapping Dysphagia Research Trends in Community Dwelling Older Adults: A Bibliometric Analysis.

Background: In recent years, research on dysphagia has gained significant traction as one of the key topics of oral health research pertaining to the aged. Numerous academics have studied dysphagia in great detail and have produced numerous excellent scientific research findings. Objective: To review the literature regarding dysphagia in community-dwelling older adults and identify the knowledge and trends using bibliometric methods. Methods: The literature on dysphagia in older adults in the community was gathered from the Web of Science Core Collection (WoSCC), with inclusion criteria specifying English-language publications. The retrieval deadline was November 28, 2022. We extracted the following data: title, year, abstract, author, keywords, institution, and cited literature, and used CiteSpace (version 6.1.R3) to visualize the data through the knowledge map, burst keyword analysis, cluster analysis, and collaborative network analysis. Results: A total of 979 articles and reviews were retrieved. Regarding productivity, the top 2 countries were the United States (n =239) and Japan (n =236). Hidetaka Wakabayashi (n =26) was one of the most prolific writers. The first paper in the frequency ranking of references cited was a white paper: European Society for Swallowing Disorders and European Union Geriatric Medicine Society white paper: oropharyngeal dysphagia as a geriatric syndrome (n =53). "Prevalence" (n =173), "risk factor" (n =119), and "aspiration pneumonia" (n =108) were the most frequently occurring keywords (excluding defining nouns). The study identified reliability, tongue pressure, home discharge, and swallowing function as research hotspots from 2020 to 2022. Conclusion: Prevalence, risk factors, and pneumonia are significant areas of study. Tongue pressure and sarcopenia are research hotspots and potential targets. In the future, research on dysphagia needs to refine strategies for prevention and control, as well as provide tertiary preventative services.

High-Performance Pomegranate-Like CuF2 Cathode Derived from Spent Lithium-Ion Batteries.

With the large-scale application of lithium-ion batteries (LIBs), a huge amount of spent LIBs will be generated each year and how to realize their recycling and reuse in a clean and effective way poses a challenge to the society. In this work, using the electrolyte of spent LIBs as solvent, we in-situ fluorinate the conductive three-dimensional porous copper foam by a facile solvent-thermal method and then coating it with a cross-linked sodium alginate (SA) layer. Benefiting from the solid-electrolyte interphase (SEI) that accommodating the volume change of internal CuF2 core and SA layer that inhibiting the dissolution of CuF2, the synthesized CuF2@void@SEI@SA cathode with a pomegranate-like structure (yolk-shell) exhibits a large reversible capacity of ~535 mAh g-1 at 0.05 A g-1 and superb cycling stability. This work conforms to the development concept of green environmental protection and comprehensively realizes the unity of environmental, social and economic benefits.