Comparative efficacy of immune checkpoint inhibitors versus chemotherapy alone in diffuse pleural mesothelioma.

BACKGROUND: This study aimed to investigate the effects of immune checkpoint inhibitors (ICIs) versus chemotherapy on the prognosis of real-world diffuse pleural mesothelioma patients in China. METHODS: Clinical data of 90 patients with diffuse pleural mesothelioma from 2019 to 2022 were collected from Harbin Medical University Cancer Hospital. Patients were divided into two groups: the ICIs-treated group (n = 46) and the chemotherapy-only group (n = 44). The efficacy and safety of immunotherapy relative to chemotherapy at different treatment stages were explored. RESULTS: The median progression-free survival (PFS) was 10.0 and 7.0 months, and the median overall survival (OS) was 24.7 and 15.8 months in the ICIs-treated group and the chemotherapy group, respectively. The ICIs-treated group showed an 11% increase in objective response rate (ORR) (52.2% vs. 41.0%) and an 8.0% increase in disease control rate (DCR) (78.3% vs. 70.0%) compared to the chemotherapy group. The Kaplan-Meier curves demonstrated significant PFS (HR: 0.61; 95% CI: 0.38-0.98; p = 0.038) and OS (HR: 0.47; 95% CI: 0.26-0.86; p = 0.011) benefits of receiving immunotherapy over chemotherapy alone. Subgroup analysis according to treatment timing showed the same trend. CONCLUSION: In patients with nonsurgical diffuse pleural mesothelioma, immunotherapy achieved better survival benefits compared to chemotherapy in both first- and second-/third-line treatments. The early addition of immunotherapy improved survival in patients with nonsurgical diffuse pleural mesothelioma.

Identification and evolution of PDK-1-like involving lamprey innate immunity.

3-phosphoinositide-dependent protein kinase-1 (PDK-1) is a key kinase regulating the activity of the PI3K/AKT pathway and a major regulator of the AGC protein kinase family. It is essential in the physiological activities of cells, embryonic development, individual development and immune response. In this study, we have identified for the first time an analogue of PDK-1 in the most primitive vertebrate, lamprey, and named it PDK-1-like. The protein sequence similarity of lamprey PDK-1-like to human, mouse, chicken, African xenopus and zebrafish PDK-1 were 64.4 %, 64.5 %, 65.0 %, 61.3 % and 63.2 %, respectively. The phylogenetic tree showed that PDK-1-like of lamprey were located at the base of the vertebrate branch, in line with the trend of biological evolution. Meanwhile, homology analysis showed that PDK-1 proteins across species shared a conserved kinase structural domain and a Pleckstrin Homology (PH) domain. Genomic synteny analysis revealed that the large-scale duplication blocks were not found in lamprey genome and neighbor genes of lamprey PDK-1-like presented dramatic differences compared with jawed vertebrates. More importantly, qPCR analysis showed that PDK-1-like was widely expressed in lamprey. Its mRNA expression levels varied in response to different pathogenic stimuli, and its expression was generally up-regulated under Polyinosinic-Polycytidylic acid (Poly(I:C)) stimulation. Pearson's correlation analysis showed that PDK-1-like was involved in co-expressed with MyD88-independent TLR-3 pathway during the immune response of lamprey, instead of MyD88-dependent TLR-3 pathway. In summary, our composite results offer valuable clues to the origin and evolution of PDK-1, and imply that PDK-1 s are among the most ancestral immune regulators in vertebrates.

The protective effects of Chromofungin in oligomeric amyloid ß42 (Aß42)-induced toxicity in neurons in Alzheimer's disease.

Oligomeric Aß42 is considered to play a harmful role in the pathophysiology of Alzheimer's disease (AD). Prolonged exposure to oligomeric Aß42 could induce neuronal damage including cellular senescence. Amelioration of Aß42-induced cellular senescence has been considered as a promising strategy for the treatment of AD. Chromofungin, a chromogranin A-derived peptide, has displayed various biological functions in different types of cells and tissues. However, the effects of Chromofungin on oligomeric Aß42-induced cellular senescence have not been previously reported. In the current study, we report a novel function of Chromofungin by showing that treatment with Chromofungin could ameliorate Aß42-induced neurotoxicity in M17 neuronal cells. The Cell Counting Kit-8 (CCK-8) assay and the lactate dehydrogenase (LDH) release experiments revealed that 0.5 and 1 mM are the optimal concentrations of Chromofungin for cell culture in M17 cells. Challenging with oligomeric Aß42 (5 µM) for 7 and 14 days led to a significant decrease in telomerase activity, which was rescued by Chromofungin dose-dependently. Additionally, the senescence-associated ß-galactosidase (SA-ß-gal) staining assay demonstrated that Chromofungin mitigated oligomeric Aß42-induced cellular senescence. Correspondingly, treatment with Chromofungin reversed the gene expression of human telomerase reverse transcriptase (hTERT), telomeric repeat-binding factor 2 (TERF2), and p21 against oligomeric Aß42 in M17 neurons. Interestingly, Chromofungin attenuated oligomeric Aß42-induced oxidative stress (OS) in M17 cells by reducing the production of intracellular reactive oxygen species (ROS) but increasing the levels of intracellular superoxide dismutase (SOD). Importantly, the presence of Chromofungin reduced the expression of cyclooxygenase2 (COX-2) as well as the generation of prostaglandin E2 (PGE2). Transduction with Ad-COX-2 impaired the effects of Chromofungin on telomerase activity and the profile of cellular senescence. Our findings suggest that Chromofungin might act as a potential agent for the treatment of AD.

Lamprey VDAC2: Suppressing hydrogen peroxide-induced 293T cell apoptosis by downregulating BAK expression.

The voltage-dependent anion channel 2 (VDAC2) is the abundant protein in the outer mitochondrial membrane. Opening VDAC2 pores leads to the induction of mitochondrial energy and material transport, facilitating interaction with various mitochondrial proteins implicated in essential processes such as cell apoptosis and proliferation. To investigate the VDAC2 in lower vertebrates, we identified Lr-VDAC2, a homologue of VDAC2 found in lamprey (Lethenteron reissneri), sharing a sequence identity of greater than 50 % with its counterparts. Phylogenetic analysis revealed that the position of Lr-VDAC2 aligns with the lamprey phylogeny, indicating its evolutionary relationship within the species. The Lr-VDAC2 protein was primarily located in the mitochondria of lamprey cells. The expression of the Lr-VDAC2 protein was elevated in high energy-demanding tissues, such as the gills, muscles, and myocardial tissue in normal lampreys. Lr-VDAC2 suppressed H2O2 (hydrogen peroxide)-induced 293 T cell apoptosis by reducing the expression levels of Caspase 3, Caspase 9, and Cyt C (cytochrome c). Further research into the mechanism indicated that the Lr-VDAC2 protein inhibited the pro-apoptotic activity of BAK (Bcl-2 antagonist/killer) protein by downregulating its expression at the protein translational level, thus exerting an anti-apoptotic function similar to the role of VDAC2 in humans.

An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.

Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.

Clinicopathological Characteristics, Survival and Prognostic Factors in Gastrointestinal Large Cell Neuroendocrine Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Gastrointestinal large cell neuroendocrine carcinoma (GILCNEC) has a low incidence but high malignancy and poor prognosis.The main purpose of this study was to thoroughly investigate its clinicopathological features, survival and prognostic factors. METHODS: Information on patients with GILCNEC was extracted from the Surveillance, Epidemiology, and End Result program, and prognostic factors were analyzed by analyzing clinicopathological data and survival functions. Finally, multivariate analysis was applied to identify independent risk factors associated with survival. RESULTS: A total of 531 individuals were screened in our study from the Surveillance, Epidemiology, and End Result database. The primary sites are mainly from the following: esophagus in 39 (7.3%) patients, stomach in 72 (13.6%) patients, hepatobiliary in 51 (9.6%) patients, pancreas in 97 (18.3%) patients, small intestines in 27 (5.1%), and colorectum in 245 (46.1%) patients. Esophagus, stomach, pancreas, and colorectum large cell neuroendocrine carcinoma (LCNEC) were more common in males (P = 0.001). Esophagus LCNEC had inferior overall survival (OS), whereas small intestine LCNEC was associated with better OS. The results of multivariate analysis showed that the American Joint Committee on Cancer Sixth Edition stage, surgery, and radiotherapy were independent prognostic indicators of OS in patients with GILCNEC (P < 0.05). CONCLUSIONS: The prognosis of patients with GILCNEC varies depending on the primary tumor site. American Joint Committee on Cancer Sixth Edition stage, surgery, and radiotherapy are independent prognostic factors of patients with GILCNEC. Although surgery and radiotherapy can prolong the survival of patients with GILCNEC, their prognosis remains poor, and further prospectively designed multicenter clinical studies are needed to indicate the decision for clinicians.

Evolutionary analysis of SLC10 family members and insights into function and expression regulation of lamprey NTCP.

The Na ( +)-taurocholate cotransporting polypeptide (NTCP) is a member of the solute carrier family 10 (SLC10), which consists of 7 members (SLC10a1-SLC10a7). NTCP is a transporter localized to the basolateral membrane of hepatocytes and is primarily responsible for the absorption of bile acids. Although mammalian NTCP has been extensively studied, little is known about the lamprey NTCP (L-NTCP). Here we show that L-NTCP follows the biological evolutionary history of vertebrates, with conserved domain, motif, and similar tertiary structure to higher vertebrates. L-NTCP is localized to the cell surface of lamprey primary hepatocytes by immunofluorescence analysis. HepG2 cells overexpressing L-NTCP also showed the distribution of L-NTCP on the cell surface. The expression profile of L-NTCP showed that the expression of NTCP is highest in lamprey liver tissue. L-NTCP also has the ability to transport bile acids, consistent with its higher vertebrate orthologs. Finally, using a farnesoid X receptor (FXR) antagonist, RT-qPCR and flow cytometry results showed that L-NTCP is negatively regulated by the nuclear receptor FXR. This study is important for understanding the adaptive mechanisms of bile acid metabolism after lamprey biliary atresia based on understanding the origin, evolution, expression profile, biological function, and expression regulation of L-NTCP.

Effects of exogenous melatonin on the osmotic regulation and antioxidant capacity of Ginkgo biloba seedlings under salt stress.

We investigated the effects of exogenous melatonin on the osmotic regulation and antioxidant capacity of 4-year-old Ginkgo biloba seedlings under salt stress. There were three treatments, with low (50 mmol·L-1), medium (100 mmol·L-1), and high (200 mmol·L-1) NaCl stress. Leaves were sprayed and the soil was watered with melatonin solution (0, 0.02, 0.1, 0.5 mmol·L-1). The results showed that saline stress significantly inhibited the osmoregulation and antioxidant capacities of G. biloba seedlings. Application of exogenous melatonin at appropriate concentrations (0.02, 0.1 mmol·L-1) under salt stress could promote plant growth, reduce the rate of electrolyte leakage, decrease the content of flavonoids and malonic dialdehyde, and enhance peroxidase and superoxide dismutase activities in leaves. High concentration (0.5 mmol·L-1) of exogenous melatonin would aggravate the oxidative and osmotic stresses. The 0.02 and 0.1 mmol·L-1 exogenous melatonin alleviated osmotic stress and oxidative stress in G. biloba seedlings under salt stress, while the 0.02 mmol·L-1 exogenous melatonin treatment had the best effect on NaCl stress alleviation. Ground diameter, branch width, branch length, electrolyte leakage rate, superoxide dismutase activity, and flavonoids content could be used as the key indices for rapid identification of the degree of salt stress in G. biloba seedlings.

1,3,6-Trigalloylglucose: A Novel Potent Anti-Helicobacter pylori Adhesion Agent Derived from Aqueous Extracts of Terminalia chebula Retz.

1,3,6-Trigalloylglucose is a natural compound that can be extracted from the aqueous extracts of ripe fruit of Terminalia chebula Retz, commonly known as "Haritaki". The potential anti-Helicobacter pylori (HP) activity of this compound has not been extensively studied or confirmed in scientific research. This compound was isolated using a semi-preparative liquid chromatography (LC) system and identified through Ultra-high-performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). Its role was evaluated using Minimum inhibitory concentration (MIC) assay and minimum bactericidal concentration (MBC) assay, scanning electron microscope (SEM), inhibiting kinetics curves, urea fast test, Cell Counting Kit-8 (CCK-8) assay, Western blot, and Griess Reagent System. Results showed that this compound effectively inhibits the growth of HP strain ATCC 700392, damages the HP structure, and suppresses the Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Importantly, it exhibits selective antimicrobial activity without impacting normal epithelial cells GES-1. In vitro studies have revealed that 1,3,6-Trigalloylglucose acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, a critical step in HP infection. These findings underscore the potential of 1,3,6-Trigalloylglucose as a targeted therapeutic agent against HP infections.

Vibration prediction and analysis of the main beam of the TBM based on a multiple linear regression model.

The vibration of tunnel boring machine (TBM) is very difficult to monitor on sites, and related research on prediction methods is rare. Based on the field tunnelling test of a TBM in the Xinjiang Ehe project, the vibration information of the main beam of the TBM under different surrounding rock conditions is collected. The relationships among the tunnelling parameters, surrounding rock parameters and vibration parameters were studied. The results show that the penetration, cutter head speed, torque and thrust are important parameters affecting TBM vibration. In addition, the field penetration index and cutter head driving power index are significantly related to the root mean square of acceleration. Based on this, a multiple regression prediction model of TBM vibration is established. The model was verified and analysed via field projects, and the relative prediction error was less than 12%. This method can be used to predict the vibration of a TBM in real time through characteristic parameters without the use of a traditional monitoring system. This approach is highly important for determining the status of TBM equipment in real time.

Electrostatically fabricated heterostructure of interfacial-polarization-enhanced Fe3O4/C/MXene for ultra-wideband electromagnetic wave absorption.

Electromagnetic (EM) pollution can disrupt the functioning of advanced electronic devices, hence it's necessary to design EM wave absorbers with high-level absorption capabilities. The Ti3C2Tx (MXene) is classified as a potential EM absorbing material; nevertheless, the lack of magnetic loss mechanism leads to its inadequate EM absorbing performance. On this basis, a novel composite design with promising EM absorption properties is hypothesized to be the integration of few-layer MXene and heterogeneous magnetic MOF derivatives (Fe3O4/C) with complementary advantages. Herein, we synthesized two-dimensional (2D) interfacial-polarization-enhanced MXene hybrid (Fe3O4/C/MXene) by electrostatic assembly. It is notable that the interfacial polarization is realized by adding a small amount of magnetic Fe3O4/C. Furthermore, the Fe3O4/C/ MXene demonstrates an astonishing effective absorption bandwidth (EAB) of 10.7 GHz and an excellent EM wave absorption performance (RLmin) of -66.9 dB. Moreover, the radar cross section (RCS) of Fe3O4/C/MXene is lower than -15.1 dB m2 from -90° to 90° with a minimum RCS value of -52.6 dB m2 at 32°. In addition, the significant attenuation of the EM wave is due to the synergistic effect of improved impedance matching, dielectric loss, and magnetic loss. Thus, the magnetized Fe3O4/C/MXene hybrid is expected to emerge as a strong contender for high-performance EM wave absorbers.

Safety and efficacy of apatinib in combination with chemotherapy with or without immunotherapy versus chemotherapy alone as first-line treatment for advanced gastric cancer.

The specific first-line regimen for advanced gastric cancer (GC) is still controversial. The benefit of apatinib for first-line treatment of advanced GC remains unknown and needs to be further explored. Eighty-two patients with advanced GC treated in our institution from October 2017 to March 2023 were retrospectively reviewed. All individuals had her-2 negative GC and had received at least two cycles of first-line treatment, including 44 patients in the combination treatment group (apatinib in combination with chemotherapy with or without immunotherapy) and 38 patients in the simple chemotherapy group. We evaluated the efficacy and safety of apatinib in combination with chemotherapy with or without immunotherapy in the first-line treatment of advanced GC by comparing the efficacy, progression-free survival (PFS), and adverse events in two groups of patients. The median PFS of the simple chemotherapy group was 9.25 months (95% confidence interval (CI), 6.1-11.2 months), and that of the combination treatment group was 10.9 months (95% CI, 7.9-15.8 months), which was 1.65 months longer than the simple chemotherapy group. Statistically significant differences are shown (P = 0.022). The objective response rate (ORR) of the combination treatment group was 65.9%, and 36.8% in the simple chemotherapy group. Statistically significant differences are shown (P = 0.014). No serious (Grade IV) adverse events occurred in either group. Our study indicates that apatinib in combination with chemotherapy with or without immunotherapy as first-line treatment for advanced GC exhibits good anti-tumor activity and is well tolerated by patients.

Identification of antibacterial activity of liver-expressed antimicrobial peptide 2 (LEAP2) from primitive vertebrate lamprey.

Liver-expressed antimicrobial peptide 2 (LEAP2) is a member of the antimicrobial peptides family and plays a key role in the innate immune system of organisms. LEAP2 orthologs have been identified from a variety of fish species, however, its function in primitive vertebrates has not been clarified. In this study, we cloned and identified Lc-LEAP2 from the primitive jawless vertebrate lamprey (Lethenteron camtschaticum) which includes a 25 amino acids signal peptide and a mature peptide of 47 amino acids. Although sequence similarity was low compared to other species, the mature Lc-LEAP2 possesses four conserved cysteine residues, forming a core structure with two disulfide bonds between the cysteine residues in the relative 1-3 (Cys 58 and Cys 69) and 2-4 (Cys 64 and Cys 74) positions. Lc-LEAP2 was most abundantly expressed in the muscle, supraneural body and buccal gland of lamprey, and was significantly upregulated during LPS and Poly I:C stimulations. The mature peptide was synthesized and characterized for its antibacterial activity against different bacteria. Lc-LEAP2 possessed inhibition of a wide range of bacteria with a dose-dependence, disrupting the integrity of bacterial cell membranes and binding to bacterial genomic DNA, although its inhibitory function is weak compared to that of higher vertebrates. These data suggest that Lc-LEAP2 plays an important role in the innate immunity of lamprey and is of great value in improving resistance to pathogens. In addition, the antimicrobial mechanism of LEAP2 has been highly conserved since its emergence in primitive vertebrates.

Neurobiological Underpinnings of Hyperarousal in Depression: A Comprehensive Review.

Patients with major depressive disorder (MDD) exhibit an abnormal physiological arousal pattern known as hyperarousal, which may contribute to their depressive symptoms. However, the neurobiological mechanisms linking this abnormal arousal to depressive symptoms are not yet fully understood. In this review, we summarize the physiological and neural features of arousal, and review the literature indicating abnormal arousal in depressed patients. Evidence suggests that a hyperarousal state in depression is characterized by abnormalities in sleep behavior, physiological (e.g., heart rate, skin conductance, pupil diameter) and electroencephalography (EEG) features, and altered activity in subcortical (e.g., hypothalamus and locus coeruleus) and cortical regions. While recent studies highlight the importance of subcortical-cortical interactions in arousal, few have explored the relationship between subcortical-cortical interactions and hyperarousal in depressed patients. This gap limits our understanding of the neural mechanism through which hyperarousal affects depressive symptoms, which involves various cognitive processes and the cerebral cortex. Based on the current literature, we propose that the hyperconnectivity in the thalamocortical circuit may contribute to both the hyperarousal pattern and depressive symptoms. Future research should investigate the relationship between thalamocortical connections and abnormal arousal in depression, and explore its implications for non-invasive treatments for depression.

[Genetic diversity analysis and fingerprinting of 175 Chimonanthus praecox germplasm based on SSR molecular marker].

The elucidation of resources pertaining to the Chimonanthus praecox varieties and the establishment of a fingerprint serve as crucial underpinnings for advancing scientific inquiry and industrial progress in relation to C. praecox. Employing the SSR molecular marker technology, an exploration of the genetic diversity of 175 C. praecox varieties (lines) in the Yanling region was conducted, and an analysis of the genetic diversity among these varieties was carried out using the UPDM clustering method in NTSYSpc 2.1 software. We analyzed the genetic structure of 175 germplasm using Structure v2.3.3 software based on a Bayesian model. General linear model (GLM) association was utilized to analyze traits and markers. The genetic diversity analysis revealed a mean number of alleles (Na) of 6.857, a mean expected heterozygosity (He) of 0.496 3, a mean observed heterozygosity (Ho) of 0.503 7, a mean genetic diversity index of Nei՚s of 0.494 9, and a mean Shannon information index of 0.995 8. These results suggest that the C. praecox population in Yanling exhibits a rich genetic diversity. Additionally, the population structure and the UPDM clustering were examined. In the GLM model, a total of fifteen marker loci exhibited significant (P < 0.05) association with eight phenotypic traits, with the explained phenotypic variation ranging from 14.90% to 36.03%. The construction of fingerprints for C. praecox varieties (lines) was accomplished by utilizing eleven primer pairs with the highest polymorphic information content, resulting in the analysis of 175 SSR markers. The present study offers a thorough examination of the genetic diversity and SSR molecular markers of C. praecox in Yanling, and establishes a fundamental germplasm repository of C. praecox, thereby furnishing theoretical underpinnings for the selection and cultivation of novel and superior C. praecox varieties, varietal identification, and resource preservation and exploitation.

Research on prevention and control technology of classified rockburst in TBM construction of deeply buried tunnels.

Rock blasting and other geological disasters occur frequently in the TBM construction of deeply buried tunnels and seriously threaten construction safety and progress. Therefore, it is extremely important to conduct scientific research for effective prevention and control of rockbursts in construction. Based on a large number of field rockburst data, this study analyses the influence of rockburst on construction safety and efficiency by using statistical theory and summarizes the temporal and spatial characteristics of rockburst time, location and influence range. Using these results, combined with the characteristics of the TBM structure and construction method, classification prevention and control objectives, theoretical criteria and prevention and control technology of rock bursts are proposed. A theoretical system of classified prevention and control of rockburst is constructed, which is cooperatively controlled by microseismic monitoring, TBM equipment, TBM excavation and support measures. The system is verified to provide practical protection, demonstrating that this report provides an important reference for the prevention and control of rock bursts in ultradeep tunnels.

Effective On-Line Performance Modulation and Efficient Continuous Preparation of Ultra-Long Twisted and Coiled Polymer Artificial Muscles for Engineering Applications.

Artificial muscle is a kind of thread-like actuator that can produce contractile strain, generate force, and output mechanical work under external stimulations to imitate the functions and achieve the performances of biological muscles. It can be used to actuate various bionic soft robots and has broad application prospects. The electrically controlled twisted and coiled polymer (TCP) artificial muscles, with the advantages of high power density, large stroke and low driving voltage, while also being electrolyte free, are the most practical. However, the relationship between the muscle performances and its preparation parameters is not very clear yet, and the complete procedure of designing and preparing TCP muscles according to actual needs has not been established. Besides, current preparation approaches are very time-consuming and cannot make ultra-long TCP muscles. These problems greatly limit wide applications of TCP artificial muscles. In this study, we studied and built the relationship between the actuating performances of TCP muscles and their preparation parameters, so that suitable TCP muscles can be easily designed and prepared according to actual requirements. Moreover, an efficient preparation method integrating one-step annealing technique has been developed to realize on-line performance modulation and continuous fabrication of ultra-long TCP muscles. By graphically assembling long muscles on heat-resist films, we designed and produced a series of fancy soft robots (butterfly, flower, starfish), which can perform various bionic movements and complete specific tasks. This work has achieved efficient on-demand preparation and large-scale assembly of ultra-long TCP muscles, laying solid foundations for their engineering applications in soft robot field.

Exploring the Multiple Roles of Notch1 in Biological Development: An Analysis and Study Based on Phylogenetics and Transcriptomics.

At present, there is a research gap concerning the specific functions and mechanisms of the Notch gene family and its signaling pathway in jawless vertebrates. In this study, we identified a Notch1 homologue (Lr. Notch1) in the Lethenteron reissneri database. Through bioinformatics analysis, we identified Lr. Notch1 as the likely common ancestor gene of the Notch gene family in higher vertebrates, indicating a high degree of conservation in the Notch gene family and its signaling pathways. To validate the biological function of Lr. Notch1, we conducted targeted silencing of Lr. Notch1 in L. reissneri and analyzed the resultant gene expression profile before and after silencing using transcriptome analysis. Our findings revealed that the silencing of Lr. Notch1 resulted in differential expression of pathways and genes associated with signal transduction, immune regulation, and metabolic regulation, mirroring the biological function of the Notch signaling pathway in higher vertebrates. This article systematically elucidated the origin and evolution of the Notch gene family while also validating the biological function of Lr. Notch1. These insights offer valuable clues for understanding the evolution of the Notch signaling pathway and establish a foundation for future research on the origin of the Notch signaling pathway, as well as its implications in human diseases and immunomodulation.