Notch信号通路——对健康和疾病的机械论观点

The Notch signaling pathway is evolutionarily conserved across metazoan species and plays key roles in many physiological processes.The Notch receptor is activated by two families of canonical ligands(Deltalike and Serrate/Jagged)where both ligands and receptors are single-pass transmembrane proteins usually with large extracellular domains,relative to their intracellular portions.Upon interaction of the core binding regions,presented on opposing cell surfaces,formation of the receptor/ligand complex initiates force-mediated proteolysis,ultimately releasing the transcriptionally-active Notch intracellular domain.This review focuses on structural features of the extracellular receptor/ligand complex,the role of posttranslational modifications in tuning this complex,the contribution of the cell membrane to ligand function,and insights from acquired and genetic diseases.

深低温保存下高效抗冻多肽的合理设计和机理探讨

The development of effective antifreeze peptides to control ice growth has attracted a significant amount of attention yet still remains a great challenge.Here,we propose a novel design method based on in-depth investigation of repetitive motifs in various ice-binding proteins(IBPs)with evolution analysis.In this way,several peptides with notable antifreeze activity were developed.In particular,a designed antifreeze peptide named AVD exhibits ideal ice recrystallization inhibition(IRI),solubility,and biocompatibility,making it suitable for use as a cryoprotective agent(CPA).A mutation analysis and molecular dynamics(MD)simulations indicated that the Thr6 and Asn8 residues of the AVD peptide are fundamental to its ice-binding capacity,while the Ser18 residue can synergistically enhance their interaction with ice,revealing the antifreeze mechanism of AVD.Furthermore,to evaluate the cryoprotection potential of AVD,the peptide was successfully employed for the cryopreservation of various cells,which demonstrated significant post-freezing cell recovery.This work opens up a new avenue for designing antifreeze materials and provides peptide-based functional modules for synthetic biology.

Liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence

Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.

Improvement in Tol2 transposon for efficient large-cargo capacity transgene applications in cultured cells and zebrafish(Danio rerio)

Most viruses and transposons serve as effective carriers for the introduction of foreign DNA up to 11 kb into vertebrate genomes.However,their activity markedly diminishes with payloads exceeding 11 kb.Expanding the payload capacity of transposons could facilitate more sophisticated cargo designs,improving the regulation of expression and minimizing mutagenic risks associated with molecular therapeutics,metabolic engineering,and transgenic animal production.In this study,we improved the Tol2 transposon by increasing protein expression levels using a translational enhancer(QBI SP163,ST)and enhanced the nuclear targeting ability using the nuclear localization protein H2B(SHT).The modified Tol2 and ST transposon efficiently integrated large DNA cargos into human cell cultures(H1299),comparable to the well-established super PiggyBac system.Furthermore,mRNA from ST and SHT showed a significant increase in transgene delivery efficiency of large DNA payloads(8 kb,14 kb,and 24 kb)into zebrafish(Danio rerio).This study presents a modified Tol2 transposon as an enhanced nonviral vector for the delivery of large DNA payloads in transgenic applications.

Model informed precision medicine of Chinese herbal medicines formulas-A multi-scale mechanistic intelligent model

Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.

New food sources and production systems:a comparison of international regulations and China’s advancements in novel foods with synthetic biology

The global shift towards sustainable food systems has sparked innovations in food sources and production systems,including cell-based meat,plant-based food products,precision fermentation,and 3D food printing.These advancements pose regulatory challenges and opportunities,with China emerging as a critical player in adopting and regulating new food technologies.This review explores the international landscape of new food sources and production systems(NFPS),focusing on China’s role and regulatory approaches compared to global practices.Through this comparative analysis,we aim to contribute to the ongoing dialogue on food safety regulation,offering insights and recommendations for policymakers,industry stakeholders,and researchers engaged in the global food system’s evolution.This comprehensive overview underscores the dynamic nature of regulatory frameworks governing NFPS,highlighting the international efforts to ensure food safety,consumer protection,and the sustainable evolution of the food industry.

Turnip mosaic virus pathogenesis and host resistance mechanisms in Brassica

Turnip mosaic virus(TuMV)is a devastating potyvirus pathogen that infects a wide variety of both cultivated and wild Brassicaceae plants.We urgently need more information and understanding of TuMV pathogenesis and the host responses involved in disease development in cruciferous crops.TuMV displays great versatility in viral pathogenesis,especially in its replication and intercellular movement.Moreover,in the coevolutionary arms races between TuMV and its hosts,the virus has evolved to co-opt host factors to facilitate its infection and counter host defense responses.This review mainly focuses on recent advances in understanding the viral factors that contribute to the TuMV infection cycle and the host resistance mechanism in Brassica.Finally,we propose some future research directions on TuMV pathogenesis and control strategies to design durable TuMV-resistant Brassica crops.

Enhanced Temporal Correlation for Universal Lesion Detection

Universal lesion detection(ULD)methods for computed tomography(CT)images play a vital role in the modern clinical medicine and intelligent automation.It is well known that single 2D CT slices lack spatial-temporal characteristics and contextual information compared to 3D CT blocks.However,3D CT blocks necessitate significantly higher hardware resources during the learning phase.Therefore,efficiently exploiting temporal correlation and spatial-temporal features of 2D CT slices is crucial for ULD tasks.In this paper,we propose a ULD network with the enhanced temporal correlation for this purpose,named TCE-Net.The designed TCE module is applied to enrich the discriminate feature representation of multiple sequential CT slices.Besides,we employ multi-scale feature maps to facilitate the localization and detection of lesions in various sizes.Extensive experiments are conducted on the DeepLesion benchmark demonstrate that thismethod achieves 66.84%and 78.18%for FS@0.5 and FS@1.0,respectively,outperforming compared state-of-the-art methods.

Evolutionary Safe Padé Approximation Scheme for Dynamical Study of Nonlinear Cervical Human Papilloma Virus Infection Model

This study proposes a structure-preserving evolutionary framework to find a semi-analytical approximate solution for a nonlinear cervical cancer epidemic(CCE)model.The underlying CCE model lacks a closed-form exact solution.Numerical solutions obtained through traditional finite difference schemes do not ensure the preservation of the model’s necessary properties,such as positivity,boundedness,and feasibility.Therefore,the development of structure-preserving semi-analytical approaches is always necessary.This research introduces an intelligently supervised computational paradigm to solve the underlying CCE model’s physical properties by formulating an equivalent unconstrained optimization problem.Singularity-free safe Padérational functions approximate the mathematical shape of state variables,while the model’s physical requirements are treated as problem constraints.The primary model of the governing differential equations is imposed to minimize the error between approximate solutions.An evolutionary algorithm,the Genetic Algorithm with Multi-Parent Crossover(GA-MPC),executes the optimization task.The resulting method is the Evolutionary Safe PadéApproximation(ESPA)scheme.The proof of unconditional convergence of the ESPA scheme on the CCE model is supported by numerical simulations.The performance of the ESPA scheme on the CCE model is thoroughly investigated by considering various orders of non-singular Padéapproximants.

Novel milestones for early esophageal carcinoma:From bench to bed

Esophageal cancer(EC)is the seventh most common cancer worldwide,and esophageal squamous cell carcinoma(ESCC)accounts for the majority of cases of EC.To effectively diagnose and treat ESCC and improve patient prognosis,timely diagnosis in the initial phase of the illness is necessary.This article offers a detailed summary of the latest advancements and emerging technologies in the timely identification of ECs.Molecular biology and epigenetics approaches involve the use of molecular mechanisms combined with fluorescence quanti-tative polymerase chain reaction(qPCR),high-throughput sequencing technology(next-generation sequencing),and digital PCR technology to study endogenous or exogenous biomolecular changes in the human body and provide a decision-making basis for the diagnosis,treatment,and prognosis of diseases.The invest-igation of the microbiome is a swiftly progressing area in human cancer research,and microorganisms with complex functions are potential components of the tumor microenvironment.The intratumoral microbiota was also found to be connected to tumor progression.The application of endoscopy as a crucial technique for the early identification of ESCC has been essential,and with ongoing advancements in technology,endoscopy has continuously improved.With the advancement of artificial intelligence(AI)technology,the utilization of AI in the detection of gastrointestinal tumors has become increasingly prevalent.The implementation of AI can effectively resolve the discrepancies among observers,improve the detection rate,assist in predicting the depth of invasion and differentiation status,guide the pericancerous margins,and aid in a more accurate diagnosis of ESCC.

Construction of Molecular Biology and Experiment Case Library for Graduate Students

Molecular Biology and Experiment is considered fundamental for graduate students specializing in aquaculture at Guangdong Ocean University.This discipline focuses on the examination of the structure and function of macromolecules,including proteins and nucleic acids.Moreover,it elucidates biological phenomena and principles at the molecular level,making it an essential foundational course for students pursuing various biology majors.As a foundational course for the basic application of aquaculture,Molecular Biology and Experiment requires guidance through numerous examples and cases.However,there are several challenges to address in developing the case library.Consequently,a case library has been established to meet the course requirements of Molecular Biology and Experiment for modern graduate students,with the central goal of reforming the educational model of higher education institutions and enhancing the effectiveness and quality of talent development.This strategy is designed to nurture highly skilled professionals who can address the current needs of the industry.

Recent research progress from biological perspective on the mechanism of formation of osteoarthritis after anterior cruciate ligament injury

The anterior cruciate ligament(ACL)mainly plays a role in stabilizing the knee joint by limiting the forward translation of tibial force and rotational force at the tibial joint,and if this ligament is damaged,it will cause joint pain,limited mobility,knee instability,etc.According to related studies,the incidence of traumatic osteoarthritis(PTOA)after ACL injury is as high as 87%,although many studies have shown that patients with ACL injury are susceptible to PTOA,but the exact mechanism is currently unknown.This may be related to biological,structural,and mechanical factors caused by the ligament injury.Previous studies have shown that elevated inflammatory mediators in the joint cavity following ACL injury can lead to chondrocytes necrosis and degradation of the cartilage matrix.These potential biochemical mediators contribute to PTOA formation,and early intervention can reduce future episodes of PTOA.In recent years,many scholars have devoted themselves to studying the potential important factors and signaling pathways involved in the formation of osteoarthritis after ACL injury,and exploring its molecular mechanism,which has led to great progress in this field.This paper mainly studies and discusses the mechanism of osteoarthritis formation after ACL injury from the biological perspective.

Personalized medicine:Clinical oncology on molecular view of treatment

Cancer,the second leading global cause of death,impacts both physically and emotionally.Conventional treatments such as surgeries,chemotherapy,and radiotherapy have adverse effects,driving the need for more precise approaches.Precision medicine enables more targeted treatments.Genetic mapping,alongside other molecular biology approaches,identifies specific genes,contributing to accurate prognoses.The review addresses,in clinical use,a molecular perspective on treatment.Biomarkers like alpha-fetoprotein,beta-human chorionic gonadotropin,5-hydroxyindoleacetic acid,programmed death-1,and cytotoxic T lymphocyte-associated protein 4 are explored,providing valuable information.Bioinformatics,with an emphasis on artificial intelligence,revolutionizes the analysis of biological data,offering more accurate diagnoses.Techniques like liquid biopsy are emphasized for early detection.Precision medicine guides therapeutic strategies based on the molecular characteristics of the tumor,as evidenced in the molecular subtypes of breast cancer.Classifications allow personalized treatments,highlighting the role of trastuzumab and endocrine therapies.Despite the benefits,challenges persist,including high costs,tumor heterogeneity,and ethical issues.Overcoming obstacles requires collaboration,ensuring that advances in molecular biology translate into accessible benefits for all.

Exploration on Teaching Reform of Synthetic Biology Course Based on the New Engineering Concept

Synthetic biology is a new frontier of life science,which aims to design,transform and even synthesize organisms with engineering design concept.Doing a good job in the teaching of"synthetic biology"is of great significance to the cultivation and reserve of biotechnology professionals in China,and also has an important impact on students' employment competitiveness.Under the background of"new engineering",the course reform of"synthetic biology"was carried out in terms of the construction of teaching staff,teaching methods,students' participation and the innovation of course content,and specific reform suggestions were put forward,hoping to effectively promote the sustainable development of"synthetic biology"and effectively improve the quality of education.

Exploring the connection between BRCA2 and thyroid cancer

Background:This study investigated the multifaceted role of BRCA2(breast cancer 2)in various cancer types,with a specific focus on thyroid carcinoma(THCA).Methods:Data sets were obtained from the University of California Santa Cruz database to analyze BRCA2 expression,genetic alterations,and clinical implications.Sample filtering criteria were applied,and immunohistochemistry from the Human Protein Atlas was used to validate protein expression.Correlation analyses were used to explore associations between immune-related genes,and immunological signatures were assessed using various tools.Genetic alterations in BRCA2 were analyzed using cBioPortal,and prognostic analysis involved evaluating gene expression differences at different clinical stages of THCA.Results:In patients with THCA,differences in BRCA2 expression were observed at both the mRNA and protein levels when comparing tumor and normal tissues.Correlation studies revealed associations between BRCA2 and immune-related genes,emphasizing its potential role in modulating the tumor microenvironment.Immunological signature analyses indicated distinct frequencies of tumor-infiltrating immune cell subsets in BRCA2 high versus low tumors.Moreover,genetic alterations in BRCA2,particularly the A2738S mutation in exon 18,have been identified in patients with THCA.The prognostic analysis demonstrated a significant correlation between altered BRCA2 levels and improved overall survival in patients with THCA.Additionally,BRCA2 expression was associated with prognostic factors such as stage and N.Conclusions:This study provides a holistic exploration of BRCA2 in cancer and highlights its diverse roles in expression,immune modulation,genetic alterations,and clinical prognosis.These findings underscore the potential significance of BRCA2 as a diagnostic and prognostic marker and offer valuable insights for future research and potential clinical applications in cancer management.

Decoding Retinoblastoma: Differential Gene Expression

Background: Retinoblastoma, the most common intraocular pediatric cancer, presents complexities in its genetic landscape that necessitate a deeper understanding for improved therapeutic interventions. This study leverages computational tools to dissect the differential gene expression profiles in retinoblastoma. Methods: Employing an in silico approach, we analyzed gene expression data from public repositories by applying rigorous statistical models, including limma and de seq 2, for identifying differentially expressed genes DEGs. Our findings were validated through cross-referencing with independent datasets and existing literature. We further employed functional annotation and pathway analysis to elucidate the biological significance of these DEGs. Results: Our computational analysis confirmed the dysregulation of key retinoblastoma-associated genes. In comparison to normal retinal tissue, RB1 exhibited a 2.5-fold increase in expression (adjusted p Conclusions: Our analysis reinforces the critical genetic alterations known in retinoblastoma and unveils new avenues for research into the disease’s molecular basis. The discovery of chemoresistance markers and immune-related genes opens potential pathways for personalized treatment strategies. The study’s outcomes emphasize the power of in silico analyses in unraveling complex cancer genomics.

De Novo Synthesis of Biopaint Using Transformed Bacteria: Analysis of Spectral Intensity Trends and Comparison to Commercial Paint

Background: Commercial paint pigments contain toxic heavy metals that harm humans and pollute the environment. To mitigate these harms, ecologically safe pigments are necessary. Objective: This experiment aims to create a biopaint de-novo using transformed Escherichia coli bacteria and compare it to commercial paint. Methods: Genetically engineered E. coli bacteria producing magenta pigment were grown in petri dishes. The pigment protein was extracted, filtered, and dehydrated into a crystalline powder. This was mixed with acrylic medium to make biopaint. The biopaint and commercial paint were applied on acrylic paper;red, green, blue, and total spectral intensities were measured daily under different testing conditions. Spectral intensity variability was measured and compared using the Coefficient of Variation (CV). Trends in spectral intensity were analyzed using regression analysis. Results: The differences in the CV of biopaint to commercial paint were less than 20% under all testing conditions. Spectral intensities for both biopaint and commercial paint did not show any significant change during the testing period under the conditions of room temperature, heat, and humidity. However, under the cold testing condition, biopaint showed a slight but statistically significant (p-value Conclusion: This experiment proves that E. coli-derived pigments can be used to make biopaint which has a similar durability to commercial paint as measured by the spectral intensities.

The Limbal Niche and Its Role in Maintaining Corneal Regeneration

In recent years, stem cells have been a focal point in research designed to evaluate the efficacy of ophthalmologic therapies, specifically those for corneal conditions. The corneal epithelium is one of the few regions of the body that maintains itself using a residual stem cell population within the adjacent limbus. Stem cell movement has additionally captivated the minds of researchers due to its potential application in different body regions. The cornea is a viable model for varying methods to track stem cell migratory patterns, such as lineage tracing and live imaging from the limbus. These developments have the potential to pave the way for future therapies designed to ensure the continuous regeneration of the corneal epithelium following injury via the limbal stem cell niche. This literature review aims to analyze the various methods of imaging used to understand the limbal stem cell niche and possible future directions that might be useful to consider for the better treatment and prevention of disorders of the cornea and corneal epithelium. .

Circular RNA: The evolving potential in the disease world

Circular RNAs(circRNAs),a new star of noncoding RNAs,are a group of endogenous RNAs that form a covalently closed circle and occur widely in the mammalian genome.Most circRNAs are conserved throughout species and fre-quently show stage-specific expression during various stages of tissue develop-ment.CircRNAs were a mystery discovery,as they were initially believed to be a product of splicing errors;however,subsequent research has shown that ci-rcRNAs can perform various functions and help in the regulation of splicing and transcription,including playing a role as microRNA(miRNA)sponges.With the application of high throughput next-generation technologies,circRNA hotspots were discovered.There are emerging indications that explain the association of circRNAs with human diseases,like cancers,developmental disorders,and in-flammation,and circRNAs may be a new potential biomarker for the diagnosis and treatment outcome of various diseases,including cancer.After the discoveries of miRNAs and long noncoding RNAs,circRNAs are now acting as a novel re-search entity of interest in the field of RNA disease biology.In this review,we aim to focus on major updates on the biogeny and metabolism of circRNAs,along with their possible/established roles in major human diseases.

Evaluation of Laboratory Request Forms Completion in a Tertiary Medical Laboratory of the Democratic Republic of Congo

Background: The inadequacy in the completeness of the Laboratory Request Form (LRF) has been reported as one of the major sources of errors during the pre-analytical step of laboratory analysis. To prevent the occurrence of such errors, this study aimed at assessing the level of completeness of LRFs. Methods: A retrospective analysis of laboratory request forms was conducted at the Clinical Biology Laboratory of the Kinshasa University Clinic, DR Congo, between November 2021 to May 2022. The LRFs were evaluated according to the completeness of all sections including administrative data of the patient, data of physician who ordered the test, relevant patient’s clinical data and data of the biological sample. Results: From a total of 2842 LRFs evaluated, none was fully completed with all required information. Particularly, patient’s clinical data including the medical history, provisional diagnosis and current treatment, were the most absent in 99% LRFs. However, two sections related to patient’s ID and prescribed test were informed in 100% LRFs. Conclusion: The results of this preanalytical audit can serve as an improvement opportunity focused on strengthening awareness about complete filling of LRF.