OPALIN is an LGI1 receptor promoting oligodendrocyte differentiation.

Leucine-rich glioma-inactivated protein 1 (LGI1), a secretory protein in the brain, plays a critical role in myelination; dysfunction of this protein leads to hypomyelination and white matter abnormalities (WMAs). Here, we hypothesized that LGI1 may regulate myelination through binding to an unidentified receptor on the membrane of oligodendrocytes (OLs). To search for this hypothetic receptor, we analyzed LGI1 binding proteins through LGI1-3 × FLAG affinity chromatography with mouse brain lysates followed by mass spectrometry. An OL-specific membrane protein, the oligodendrocytic myelin paranodal and inner loop protein (OPALIN), was identified. Conditional knockout (cKO) of OPALIN in the OL lineage caused hypomyelination and WMAs, phenocopying LGI1 deficiency in mice. Biochemical analysis revealed the downregulation of Sox10 and Olig2, transcription factors critical for OL differentiation, further confirming the impaired OL maturation in Opalin cKO mice. Moreover, virus-mediated re-expression of OPALIN successfully restored myelination in Opalin cKO mice. In contrast, re-expression of LGI1-unbound OPALIN_K23A/D26A failed to reverse the hypomyelination phenotype. In conclusion, our study demonstrated that OPALIN on the OL membrane serves as an LGI1 receptor, highlighting the importance of the LGI1/OPALIN complex in orchestrating OL differentiation and myelination.

Oxidative stress is involved in immunosuppression and macrophage regulation in glioblastoma.

Oxidative stress dually affected cancer progression, while its effect on glioblastomas remained unclear. Herein, we clustered the multicenter glioblastoma cohorts based on the oxidative-stress-responsive genes (OSS) expression. We found that cluster 2 with high OSS levels suffered a worse prognosis. Functional analyses and immune-related analyses results exhibited that M2-like pro-tumoral macrophages and neutrophils were enriched in cluster 2, while Natural killer cells' infiltration was decreased. The increased M2-like pro-tumoral macrophages in cluster 2 was confirmed by immunofluorescence. An integrated single-cell analysis validated the malignant features of cluster 2 neoplastic cells and discovered their crosstalk with M2-like pro-tumoral macrophages. Moreover, we observed that SOD3 knockdown might decrease the M2-like pro-tumoral transformation of macrophage in vitro and in vivo. Comprehensively, we revealed oxidative stress' prognostic and immunosuppressive potential in glioblastoma and discovered SOD3's potential role in regulating macrophage M2-like pro-tumoral transformation.

Extracellular vesicles deviced from hypoxia-3D-GMSCs rescue the mitochondrial dysfunction of aging-GMSCs.

Mesenchymal stem cells (MSCs) are ubiquitous multipotent cells exhibiting significant therapeutic potential for various diseases. It is generally accepted that clinical application requires massive expansion of MSCs, which is often accompanied by the occurrence of replicative senescence. Additionally, senescent MSCs exhibit significantly reduced proliferation, differentiation, and therapeutic potential. The scale-up of MSCs production and cellular senescence are major challenges for translational applications. This study first collected extracellular vesicles (EVs) from gingival MSCs (GMSCs) under hypoxia preconditioning combined with 3D dynamic culture (obtained EVs designed as H-3D-EVs). Subsequently, we further explored the effects and mechanisms of H-3D-EVs on aging-GMSCs. The results showed that H-3D-EVs improved the proliferation ability and cell activity of aging-GMSCs, and ameliorated their senescence. mRNA sequencing reveals transcriptomic changes in aging-GMSCs. It was found that H-3D-EVs up-regulated genes related to mitochondrial dynamics, cell cycle, and DNA repair, while down-regulated aging-related genes. Furthermore, we verified that H-3D-EVs corrected the mitochondrial dysfunction of aging-GMSCs by improving mitochondrial dynamics. In summary, this study provides a promising strategy for improving the culture methods of GMSCs and avoiding its senescence in large-scale production.

Machine learning-based tumor-infiltrating immune cell-associated lncRNAs for predicting prognosis and immunotherapy response in patients with glioblastoma.

Long noncoding ribonucleic acids (RNAs; lncRNAs) have been associated with cancer immunity regulation. However, the roles of immune cell-specific lncRNAs in glioblastoma (GBM) remain largely unknown. In this study, a novel computational framework was constructed to screen the tumor-infiltrating immune cell-associated lncRNAs (TIIClnc) for developing TIIClnc signature by integratively analyzing the transcriptome data of purified immune cells, GBM cell lines and bulk GBM tissues using six machine learning algorithms. As a result, TIIClnc signature could distinguish survival outcomes of GBM patients across four independent datasets, including the Xiangya in-house dataset, and more importantly, showed superior performance than 95 previously established signatures in gliomas. TIIClnc signature was revealed to be an indicator of the infiltration level of immune cells and predicted the response outcomes of immunotherapy. The positive correlation between TIIClnc signature and CD8, PD-1 and PD-L1 was verified in the Xiangya in-house dataset. As a newly demonstrated predictive biomarker, the TIIClnc signature enabled a more precise selection of the GBM population who would benefit from immunotherapy and should be validated and applied in the near future.

Antiresonant fiber-enhanced Raman spectroscopy gas sensing with 1†ppm sensitivity.

Antiresonant hollow-core fiber (AR-HCF) exhibits unprecedented optical performance in low transmission attenuation, broad transmission bandwidth, and single spatial mode quality. However, due to its lower numerical aperture, when utilizing the Fiber-Enhanced Raman Spectroscopy (FERS) principle for gas detection, the efficiency of AR-HCF in collecting Raman signals per unit length is significantly lower than that of hollow-core photonic crystal fiber. Nonetheless, AR-HCF effectively suppresses higher-order modes and offers bandwidth in hundreds of nanometers. By increasing the length of AR-HCF, its advantages can be effectively harnessed, leading to a considerable enhancement in the system's ability for low-concentration gas detection. We combine the nodeless antiresonant hollow-core fiber and Raman spectroscopy for enhanced Raman gas sensing in a forward scattering measurement configuration to investigate the attenuation behavior of the silica background signals. The silica background attenuation behavior enables the low baseline of the gas Raman spectroscopy and extends the integration time of the system. In addition, a convenient spatial filtering method is investigated. A multimode fiber with a suitable core diameter was employed to transmit the signal so that the fiber end face plays the role of pinhole, thus filtering the silica signal and reducing the baseline. The natural isotopes 12C16O2, 13C16O2, and 12C18O16O in ambient air can be observed using a 5-meter-long AR-HCF at 1 bar with a laser output power of 1.8 W and an integration time of 300 seconds. Limits of detection have been determined to be 0.5 ppm for 13C16O2 and 1.2 ppm for 12C16O2, which shows that the FERS with AR-HCF has remarkable potential for isotopes and multigas sensing.

Application of Organoids in Regenerative Medicine.

Regenerative medicine mainly relies on heterologous transplantation, often hindered by sample availability and ethical issues. Furthermore, patients are required to take immunosuppressive medications to prevent adverse side effects. Stem cell-derived 3D-organoid culture has provided new alternatives for transplantation and regenerative medicine. Scholars have combined organoids with tissue engineering technology to improve reproducibility, the accuracy of constitution and throughput, and genetic correction to achieve a more personalized therapy. Here, we review the available applications of organoids in regenerative medicine and the current challenges concerning this field.

Thiol-ene Click Chemistry Synthesis of L-Cysteine-Grafted Graphene Oxide As a New Corrosion Inhibitor for Q235 Steel in Acidic Environment.

l-cysteine, as an eco-friendly and nontoxic corrosion inhibitor, was directly covalently linked to the carbon/carbon double bonds of the GO flakes by a thiol-ene click reaction to avoid decreasing the number of hydrophilic oxygen-containing polar functionalities. The corrosion inhibition performances of Cys-GO toward Q235 steel (QS) in diluted hydrochloric acid were studied by electrochemical methods. The corrosion was a charge transfer-controlled process, and Cys-GO manifested as a mixed-type corrosion inhibitor. The corrosion inhibition efficiency (η) for QS showed a first-increase-and-then-decrease trend with increasing Cys-GO concentrations. The optimum concentration of Cys-GO was 15 mg L-1, and the according η value was up to 90%. The Cys-GO adsorbed on the QS surface to form a protective barrier was responsible for the efficient corrosion inhibition. Langmuir adsorption isotherm model was fitted well with the experiment data, indicating a monolayer adsorption. Furthermore, the coordinate covalent bonds, π-back-donation effect, and electrostatic attraction were responsible for the Cys-GO adsorption on the QS surface.

How to identify biofouling species in marine and freshwater.

The identification and management of biofouling remain pressing challenges in marine and freshwater ecosystems, with significant implications for environmental sustainability and industrial operations. This comprehensive review synthesizes the current state-of-the-art in biofouling identification technologies, examining eight prominent methodologies: Microscopy Examination, Molecular Biology, Remote Sensing, Community Involvement, Ecological Methods, Artificial Intelligence, Chemical Analysis, and Macro Photography. Each method is evaluated for its respective advantages and disadvantages, considering factors such as precision, scalability, cost, and data quality. Furthermore, the review identifies current obstacles that inhibit the optimal utilization of these technologies, ranging from technical limitations and high operational costs to issues of data inconsistency and subjectivity. Finally, the review posits a future outlook, advocating for the development of integrated, standardized systems that amalgamate the strengths of individual approaches. Such advancement will pave the way for more effective and sustainable strategies for biofouling identification and management.

Mechanical Behavior Monitoring and Load Inversion Analysis of Large-Diameter Underwater Shield Tunnel during Construction.

The construction of large-diameter shield tunnels underwater involves complex variations in water and earth load outside the tunnel segment, as well as intricate mechanical responses. This study analyzes the variation laws of external loads, axial forces, and bending moments acting on the segment ring during the shield assembly and removal from the shield tail. It accomplishes this through the establishment of an on-site monitoring system based on the Internet of Things (IoT) and proposes a Bayesian-genetic algorithm model to estimate the water and earth pressure. The fluctuation section exhibits a peak load twice as high as that in the stable section. These variations are influenced by Jack thrust, shield shell force, and grouting pressure. The peak load observed in the fluctuation section is twice as high as the load observed in the stable section. During the shield tail removal process, the internal forces undergo significant fluctuations due to changes in both load and boundary conditions, and the peak value of the axial force during the fluctuation section is eight times higher than that during the stable section, while the peak value of the bending moment during the fluctuation section is five times higher than that during the stable section. The earth and water pressure calculated using the inversion analysis method, which relies on the measured internal forces, closely matches the actual measured values. The results demonstrate that the accuracy of the water and earth pressure obtained through inversion analysis is twice as high as that obtained using the full coverage pressure method. These results can serve as a valuable reference for similar projects.

APETALA2-like Floral Homeotic Protein Up-Regulating FaesAP1_2 Gene Involved in Floral Development in Long-Homostyle Common Buckwheat.

In the rosid species Arabidopsis thaliana, the AP2-type AP2 transcription factor (TF) is required for specifying the sepals and petals identities and confers a major A-function to antagonize the C-function in the outer floral whorls. In the asterid species Petunia, the AP2-type ROB TFs are required for perianth and pistil development, as well as repressing the B-function together with TOE-type TF BEN. In Long-homostyle (LH) Fagopyrum esculentum, VIGS-silencing showed that FaesAP2 is mainly involved in controlling filament and style length, but FaesTOE is mainly involved in regulating filament length and pollen grain development. Both FaesAP2 (AP2-type) and FaesTOE (TOE-type) are redundantly involved in style and/or filament length determination instead of perianth development. However, neither FaesAP2 nor FaesTOE could directly repress the B and/or C class genes in common buckwheat. Moreover, the FaesAP1_2 silenced flower showed tepal numbers, and filament length decreased obviously. Interestingly, yeast one-hybrid (Y1H) and dual-luciferase reporter (DR) further suggested that FaesTOE directly up-regulates FaesAP1_2 to be involved in filament length determination in LH common buckwheat. Moreover, the knockdown of FaesTOE expression could result in expression down-regulation of the directly target FaesAP1_2 in the FaesTOE-silenced LH plants. Our findings uncover a stamen development pathway in common buckwheat and offer deeper insight into the functional evolution of AP2 orthologs in the early-diverging core eudicots.

A review of experimental Assessment Processes of material resistance to marine and freshwater biofouling.

Biofouling presents hazards to a variety of freshwater and marine underwater infrastructures and is one of the direct causes of species invasion. These negative impacts provide a unified goal for both industry practitioners and researchers: the development of novel antifouling materials to prevent the adhesion of biofouling. The prohibition of tributyltin (TBT) by the International Maritime Organization (IMO) in 2001 propelled the research and development of new antifouling materials. However, the evaluation process and framework for these materials remain incomplete and unsystematic. This mini-review starts with the classification and principles of new antifouling materials, discussing and summarizing the methods for assessing their biofouling resistance. The paper also compiles the relevant regulations and environmental requirements from different countries necessary for developing new antifouling materials with commercial potential. It concludes by highlighting the current challenges in antifouling material development and future outlooks. Systematic evaluation of newly developed antifouling materials can lead to the emergence of more genuinely applicable solutions, transitioning from merely laboratory products to materials that can be effectively used in real-world applications.

Identification of a single cell-based signature for predicting prognosis risk and immunotherapy response in patients with glioblastoma.

This study constructed a novel gene pair signature based on bulk and single-cell sequencing samples in relative expression order within the samples. The subsequent analysis included glioma samples from Xiangya Hospital. Gene pair signatures possessed a solid ability to predict the prognosis of glioblastoma and pan-cancer. Samples having different malignant biological hallmarks were distinguished by the algorithm, with the high gene pair score group featuring classic copy number variations, oncogenic mutations, and extensive hypomethylation, mediating poor prognosis. The increased gene pair score group with a poorer prognosis demonstrated significant enrichment in tumor and immune-related signaling pathways while presenting immunological diversity. The remarkable infiltration of M2 macrophages in the high gene pair score group was validated by multiplex immunofluorescence, suggesting that combination therapies targeting adaptive and innate immunity may serve as a therapeutic option. Overall, a gene pair signature applicable to predict prognosis hopefully provides a reference to guide clinical practice.

Energy-Efficient Algorithms for Path Coverage in Sensor Networks.

Path coverage attracts many interests in some scenarios, such as object tracing in sensor networks. However, the problem of how to conserve the constrained energy of sensors is rarely considered in existing research. This paper studies two problems in the energy conservation of sensor networks that have not been addressed before. The first problem is called the least movement of nodes on path coverage. It first proves the problem as NP-hard, and then uses curve disjunction to separate each path into some discrete points, and ultimately moves nodes to new positions under some heuristic regulations. The utilized curve disjunction technique makes the proposed mechanism unrestricted by the linear path. The second problem is called the largest lifetime on path coverage. It first separates all nodes into independent partitions by utilizing the method of largest weighted bipartite matching, and then schedules these partitions to cover all paths in the network by turns. We eventually analyze the energy cost of the two proposed mechanisms, and evaluate the effects of some parameters on performance through extensive experiments, respectively.

Quantum Tunneling Effect in CsPbBr3 Multiple Quantum Wells.

Two-dimensional (2D) lead halide perovskites (LHPs) have garnered incredible attention thanks to their exciting optoelectronic properties and intrinsic strong quantum confinement effect. Herein, we carefully investigate and decipher the charge carrier dynamics at the interface between CsPbBr3 multiple quantum wells (MQWs) as the photoactive layer and TiO2 and Spiro-OMeTAD as electron and hole transporting materials, respectively. The fabricated MQWs comprise three monolayers of CsPbBr3 separated by 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP) as barriers. By varying the BCP thickness, we show that charge carrier extraction from MQWs to the corresponding extracting layer occurs through a quantum tunneling effect, as elaborated by steady-state and time-resolved photoluminescence measurements and further verified by femtosecond transient absorption experiments. Ultimately, we have investigated the impact of the barrier-thickness-dependent quantum tunneling effect on the photoelectric behavior of the synthesized QW photodetector devices. Our findings shed light on one of the most promising approaches for efficient carrier extraction in quantum-confined systems.

Recent Advances in Stimuli-Responsive Metallogels.

Recently, stimuli-responsive supramolecular gels have received significant attention because their properties can be modulated through external stimuli such as heat, light, electricity, magnetic fields, mechanical stress, pH, ions, chemicals and enzymes. Among these gels, stimuli-responsive supramolecular metallogels have shown promising applications in material science because of their fascinating redox, optical, electronic and magnetic properties. In this review, research progress on stimuli-responsive supramolecular metallogels in recent years is systematically summarized. According to external stimulus sources, stimuli-responsive supramolecular metallogels, including chemical, physical and multiple stimuli-responsive metallogels, are discussed separately. Moreover, challenges, suggestions and opportunities regarding the development of novel stimuli-responsive metallogels are presented. We believe the knowledge and inspiration gained from this review will deepen the current understanding of stimuli-responsive smart metallogels and encourage more scientists to provide valuable contributions to this topic in the coming decades.

Glioma targeted therapy: insight into future of molecular approaches.

Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males are more susceptible than females. According to the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), standard of care and prognosis of gliomas can be dramatically different. Generally, circumscribed gliomas are usually benign and recommended to early complete resection, with chemotherapy if necessary. Diffuse gliomas and other high-grade gliomas according to their molecule subtype are slightly intractable, with necessity of chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide chemotherapy define the current standard of care. Here, we discuss novel feasible or potential targets for treatment of gliomas, especially IDH-wild type glioblastoma. Classic targets such as the p53 and retinoblastoma (RB) pathway and epidermal growth factor receptor (EGFR) gene alteration have met failure due to complex regulatory network. There is ever-increasing interest in immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), tumor microenvironment, and combination of several efficacious methods. With many targeted therapy options emerging, biomarkers guiding the prescription of a particular targeted therapy are also attractive. More pre-clinical and clinical trials are urgently needed to explore and evaluate the feasibility of targeted therapy with the corresponding biomarkers for effective personalized treatment options.

Tumor buster - where will the CAR-T cell therapy 'missile' go?

Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies' clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.

Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomised controlled trials.

BACKGROUND: To investigate whether metformin monotherapy or adjunctive therapy improves the prognosis in patients with any type of cancer compared to non-metformin users (age ≥18). METHODS: Databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) and clinical trial registries ( ClinicalTrials.gov ; the World Health Organization International Clinical Trials Registry Platform) were screened for randomized, controlled trials (RCT) reporting at least progression-free survival (PFS) and/or overall survival (OS). Main outcome measures included hazard ratios (HR), and combined HRs and 95% confidence intervals (CI) were calculated using random-effects models. RESULTS: Of the 8419 records screened, 22 RCTs comprising 5943 participants were included. Pooled HRs were not statistically significant in both PFS (HR 0.97, 95% CI 0.82-1.15, I2 = 50%) and OS (HR 0.98, 95% CI 0.86-1.13, I2 = 33%) for patients with cancer between the metformin and control groups. Subgroup analyses demonstrated that metformin treatment was associated with a marginally significant improvement in PFS in reproductive system cancers (HR 0.86, 95% CI 0.74-1.00) and a significantly worse PFS in digestive system cancers (HR 1.45, 95% CI 1.03-2.04). The PFS or OS was observed consistently across maintenance dose, diabetes exclusion, median follow-up, risk of bias, and combined antitumoral therapies. CONCLUSION: Metformin treatment was not associated with cancer-related mortality in adults compared with placebo or no treatment. However, metformin implied beneficial effects in the PFS of the patients with reproductive system cancers but was related to a worse PFS in digestive system cancers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42022324672.

Natural killer cell-related gene signature predicts malignancy of glioma and the survival of patients.

BACKGROUND: Natural killer (NK) cells-based therapies are one of the most promising strategies against cancer. The aim of this study is to investigate the natural killer cell related genes and its prognostic value in glioma. METHODS: The Chinese Glioma Genome Atlas (CGGA) was used to develop the natural killer cell-related signature. Risk score was built by multivariate Cox proportional hazards model. A cohort of 326 glioma samples with whole transcriptome expression data from the CGGA database was included for discovery. The Cancer Genome Atlas (TCGA) datasets was used for validation. GO and KEGG were used to reveal the biological process and function associated with the natural killer cell-related signature. We also collected the clinical pathological features of patients with gliomas to analyze the association with tumor malignancy and patients' survival. RESULTS: We screened for NK-related genes to build a prognostic signature, and identified the risk score based on the signature. We found that NK-related risk score was independent of various clinical factors. Nature-killer cell gene expression is correlated with clinicopathological features of gliomas. Innovatively, we demonstrated the tight relation between the risk score and immune checkpoints, and found NK-related risk score combined with PD1/PDL1 patients could predict the patient outcome. CONCLUSION: Natural killer cell-related gene signature can predict malignancy of glioma and the survival of patients, these results might provide new view for the research of glioma malignancy and individual immunotherapy.

FaesAP3_1 Regulates the FaesELF3 Gene Involved in Filament-Length Determination of Long-Homostyle Fagopyrum esculentum.

The identification downstream genes of floral organ identity regulators are critical to revealing the molecular mechanisms underlying floral morphogenesis. However, a general regulatory pathway between floral organ identity genes and their downstream targets is still unclear because of the lack of studies in nonmodel species. Here, we screened a direct downstream target gene, FaesELF3, of a stamen identity transcription factor, FaesAP3_1, in long-homostyle (LH) Fagopyrum esculentum moench by using yeast one-hybrid (Y1H) and dual-luciferase reporter (DR) assays. Furthermore, FaesAP3_1-silenced LH plants that produced flowers with part stamens or anthers homeotically converted into a tepaloid structure, and FaesELF3-silenced plants that had flowers with part stamens consisting of a short filament and empty anther (male sterile anther). All these suggested that transcription factor (TF) FaesAP3_1 directly activates FaesELF3 in order to regulate filament elongation and pollen grain development in LH buckwheat. Our data also suggested that other stamen development pathways independent of FaesAP3_1 remain in F. esculentum.