Development Of Biotechnology Research Articles

Ethical reflection of Chinese scientists on the dual-use concerns of emerging medical biotechnology

Emerging medical biotechnology typically exhibits a ‘dual-use’ nature, which, while promoting human well-being, concurrently presents potential risks of misuse or abuse, thereby posing significant threats. Globally, including in China, emerging...

Electro-deformation spectroscopy: a unified method for simultaneous electrical and mechanical characterization of single cells.

The intrinsic electrical and mechanical properties of cells are not only valuable biophysical markers reflective of physiological conditions but also play important roles in the development and progression of human diseases. Existing single-cell techniques are restricted to assessing either mechanical or electrical properties. We introduce the development of electro-deformation spectroscopy (EDS), namely the frequency-dependent electro-deformation, as a new method for simultaneous electrical and mechanical characterization of individual cells in suspension. To facilitate the practical use of this technology, we developed a testing procedure that evaluates red blood cells (RBCs) directly from whole blood in a simple microfluidic system, employing an electric field magnitude of 34 kV/m over a frequency range of 15 MHz to 100 kHz. The EDS measurement is performed under stationary conditions without special cell stabilization, at a moderate throughput of 50-100 cells per minute. We develop an experimental-computational framework to decouple cell electromechanics by optimizing the most suitable parameters of the relative permittivity of cell membrane, cytoplasm electrical conductivity, and membrane shear modulus. This technique, tested on RBCs from 4 healthy human samples, revealed membrane relative permittivity of 3.6 - 5.8, membrane shear modulus of 2.2 - 2.8 µN/m, and cytoplasm conductivity of 0.47 - 0.81 S/m. EDS analysis identifies the marked intrasample heterogeneity and individual variability in both cellular electrical and mechanical properties. The EDS framework can be readily used to test RBCs across different species, pathological states, and other cell types of similar structures as RBCs. STATEMENT OF SIGNIFICANCE: : This work introduces electro-deformation spectroscopy (EDS) as a unified method for simultaneous electrical and mechanical characterization of single cells in suspension. This is the first-of-its-kind technology for such purposes. EDS can be performed in a simple microfluidic system with minimal sample preparation, making it a convenient and powerful tool for label-free, non-invasive single-cell analysis. We validate the applicability of EDS by measuring the intrasample heterogeneity and individual variability based on the electromechanical parameters of interest for human red blood cells. Single-cell EDS has the potential to enable rapid and reliable detection of cellular changes by diseases or drug treatments and provide insights into the fundamental bioelectromechanical mechanisms of cellular adaptation and dysfunction. This work advances the field of single-cell analysis and contributes to the development of biomaterials and biotechnologies based on cellular electromechanics.

Development of a hydroponic device using potassium Ion-Selective electrode and neural network technology

The rapid development of modern agricultural biotechnology and information technology has become a key driver of modern agricultural growth. The demand for ion detection is prevalent in all aspects of agriculture. This study details the research on an ion sensor agricultural system using potassium (K) ion-selective electrodes (ISEs). The main emphasis is on the application of artificial neural networks (ANNs) for driving ISE development of accuracy. ISEs based on solid contact with metal oxides, specifically manganese dioxide, are studied. Moreover, the design details of an ion signal acquisition device using the NI-9205 acquisition card and LabVIEW are presented. Finally, based on experimental results of nutrient solution samples, ANNs show better performance than the multiple linear regression method. The mean relative error of K-ISE detection was maintained within 4%. This study thoroughly discusses ISE technology to promote its adoption in agriculture.

Nitrogen stress-induced modulation of antimicrobial and antioxidant activities in Aphanothece sp.: Insights from phytochemical profiling and molecular docking

The modulation of nutrient availability represents a critical factor influencing the metabolic pathways and production of bioactive compounds in algae. This study aimed to examine the impact of nitrogen stress on the antimicrobial and antioxidant properties, phytochemical composition, and molecular docking assessments of the cyanobacterium Aphanothece sp. The results demonstrated that Aphanothece sp. when cultivated under conditions of nitrogen deficiency, exhibited markedly elevated antimicrobial and antioxidant activity compared to the control. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of the extracts obtained from algae on E. coli ATCC 25922 were found to be 25 mg mL−1 when the sample was grown in nitrogen medium and 6.25 mg mL−1 when grown in a nitrogen-free medium. The IC50 value obtained from DPPH free radical scavenging assay changed from 137.30 ± 16.22 mg mL−1 to 20.07 ± 1.55 mg mL−1 in nitrogen-free medium. According to the results of GC–MS analysis, the major components in the extract obtained from the algae grown in the nitrogen-free environment were 13,16-Octadecadiynoic acid, methyl ester (35.10 %) and Hexadecanoic acid, methyl ester (22.65 %), while the major components in the extract obtained from the algae grown in nitrogen-containing medium were Protopine (65.68 %) and 3,6,9,12,15-Pentaoxabicyclo(15.3.1)henicosa-1(21),17,19-triene-2,16-dione (12.15 %). The findings suggest a range of binding energies and interaction profiles for the compounds in the extracts with their molecular targets, which may have implications for their potential significance in therapeutic applications. The results of this study indicate that nitrogen stress can be employed as a strategic tool to enhance the production of valuable bioactive compounds in Aphanothece sp., thereby underscoring its potential applications in biotechnology and drug development.

An efficient and easily obtainable butelase variant for chemoenzymatic ligation and modification of peptides and proteins

The expanding field of site-specific ligation of proteins and peptides has catalyzed the development of novel methods that enhance molecular modification. Among these methods, enzymatic strategies have emerged as dominant due to their specificity and efficiency in modifying proteins under mild conditions. Asparaginyl endopeptidase is a group of cyclotide-producing cysteine proteases from plants. These plant cysteine proteases, known for their specificity, effectively recognize the tripeptide motif (Asx-Xaa-Yaa) and cleave at the C-terminal side of Asx residues, forming acyl-enzyme intermediates that facilitate transpeptidation. Butelase 1 stands out as the most efficient AEP for protein engineering, yet challenges in its expression and purification limit its accessibility for widespread research and industrial use. To address these challenges, we engineered a new, catalytically efficient variant of Butelase 1, Butelase AY, by mutating the gatekeeping residues Val237Ala and Thr238Tyr within the LAD-1 region. These modifications significantly enhanced the stability and yield of Butelase AY, allowing for successful application in various peptide and protein engineering tasks. Butelase AY was tested on the peptide GLGKY, the globular protein GFP, and the intrinsically disordered protein α-synuclein, effectively labeling them with a fluorescent probe. Notably, Butelase AY maintained its efficiency with substrates containing unnatural amino acids, making it a promising candidate for biorthogonal applications. Importantly, the mutations did not compromise the enzyme’s specificity, as it continued to process model peptides and native protein substrates with N-term NHV recognition motifs effectively. In conclusion, Butelase AY presents a novel recombinant tool for diverse protein labeling and modifications, particularly in biorthogonal strategies. This innovation has the potential to expand applications in biotechnology and therapeutic development, ultimately revolutionizing protein engineering and its utility in synthetic biology.

Application and research progress of synthetic lethality in the development of anticancer therapeutic drugs.

With the tremendous success of the PARP inhibitor olaparib in clinical practice, synthetic lethality has become an important field for the discovery and development of anticancer drugs. More and more synthetic lethality targets have been discovered with the rapid development of biotechnology in recent years. Currently, many drug candidates that were designed and developed on the basis of the concept of synthetic lethality have entered clinical trials. Taking representative synthetic lethal targets Poly ADP-ribose polymerase 1 (PARP1), Werner syndrome helicase (WRN) and protein arginine methyltransferase 5 (PRMT5) as examples, this article briefly discusses the application and research progress of synthetic lethality in the development of anticancer drugs.

EfficientNet-resDDSC: A Hybrid Deep Learning Model Integrating Residual Blocks and Dilated Convolutions for Inferring Gene Causality in Single-Cell Data.

Gene Regulatory Networks (GRNs) reveal complex interactions between genes in organisms, crucial for understanding the life system's operation. The rapid development of biotechnology, especially single-cell RNA sequencing (scRNA-seq), has generated a large amount of scRNA-seq data, which can be analyzed to explore the regulatory relationships between genes at the single-cell level. Previous models used to construct GRNs mainly aim at constructing associative relationships between genes, but usually fail to accurately reveal the causality between genes. Therefore, we present a hybrid deep learning model called EfficientNet-resDDSC (the EfficientNet with Residual Blocks and Depthwise Separable Dilated Convolutions) to infer causality between genes. The model inherits the basic structure of EfficientNet-B0 and incorporates residual blocks as well as dilated convolutions. The model's ability to extract low-level features at the primary stage is enhanced by introducing residual blocks. The model combines Depthwise Separable Convolution (DSC) in the inverted linear bottleneck layers with the dilated convolutions to expand the model's receptive fields without increasing the computational effort. This design enables the model to comprehensively reveal potential relationships among different genes in high-dimensional and high-noise single-cell data. In comparison with the five existing deep learning network models, EfficientNet-resDDSC's overall performance is significantly better than others on four datasets. In this study, EfficientNet-resDDSC was further applied to construct GRNs for breast cancer patients, focusing on the related regulatory genes of the key gene BRCA1, which contributes to the advancement of breast cancer research and treatment strategies.

The comparison between different therapies of Systemic Lupus Erythematosus

Abstract. The immune system has three basic functions: defense, surveillance and homeostasis. It helps us monitoring and timely eliminate mutant cells and distinguishing between alien components to maintain self-stability. However, once it loses these abilities, it could cause the autoimmune disease. In this article, I mainly discuss about the Systemic Lupus Erythematosus (SLE), a type of autoimmune diseases which is mediated by type hypersensitivity. SLE patients suffer from chronic inflammatory responses, leading to tissue damage and organ dysfunction. Therefore, purpose of therapeutic schedule is to inhibit the overactive immune system and relieve the inflammatory response. Nowadays, there are three major therapies: Glucocorticoids (GC), immunosuppression agents and belimumab. Glucocorticoids suppresses inflammatory responses and generate anti-inflammatory factors. Immunosuppression agents can not only control SLE and raise the survival rate of long-term prognosis for SLE patients. Belimumab inhibits the survival of B cells by obstructing the interaction between soluble B cell activating factor (BAFF or BLys) and receptors on B cells. This action promotes the apoptosis of auto-reactive B cells, leading to a decrease in auto-antibodies present in the serum. With the development of biotechnology, more and more advanced treatments have emerged and brings new hope to SLE patients.

How do you anticipate computational protein design will change biotechnology and therapeutic development?

How do you anticipate computational protein design will change biotechnology and therapeutic development?

Recent Progress in Nanomaterial-Based Surface-Enhanced Raman Spectroscopy for Food Safety Detection.

Food safety has recently become a widespread concern among consumers. Surface-enhanced Raman scattering (SERS) is a rapidly developing novel spectroscopic analysis technique with high sensitivity, an ability to provide molecular fingerprint spectra, and resistance to photobleaching, offering broad application prospects in rapid trace detection. With the interdisciplinary development of nanomaterials and biotechnology, the detection performance of SERS biosensors has improved significantly. This review describes the advantages of nanomaterial-based SERS detection technology and SERS's latest applications in the detection of biological and chemical contaminants, the identification of foodborne pathogens, the authentication and quality control of food, and the safety assessment of food packaging materials. Finally, the challenges and prospects of constructing and applying nanomaterial-based SERS sensing platforms in the field of food safety detection are discussed with the aim of early detection and ultimate control of foodborne diseases.

Platelet membrane coated r-SAK to improve thrombolytic efficacy by targeting thrombus

Abstract Background Thrombolytic therapy is one of the most effective treatments to achieve rapid thrombus clearance and recanalization of blocked vessels in thrombotic diseases. However, the application of thrombolytic strategy has been limited due to unsatisfied thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications.[1] With the development of nanotechnology and biotechnology, platelet membrane nanoparticles have been developed to enable the targeted delivery of thrombolytic agents to local thrombus sites.[2] Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology. In this study, platelet membrane coated r-SAK (PLT-r-SAK) was constructed, and its thrombolytic efficacy was evaluated in in-vitro and in-vivo experiments. Purpose We aimed to construct a thrombus-targeting agent of PLT-r-SAK and investigate its thrombolytic efficacy. Methods PLT-r-SAK was prepared by encapsulating r-SAK into platelet membrane vesicles using a membrane extrusion method. An in-vitro thrombolytic experiment was performed to examine the thrombolytic efficacy of PLT-r-SAK, and a totally occluded femoral artery thrombosis model of rabbit was developed to evaluate the in-vivo thrombolytic efficacy of PLT-r-SAK. The changes in femoral artery pressure were adopted to assess the vessel opening status. Besides, the effect of the antiplatelet drugs on the thrombolytic efficacy of PLT-r-SAK was explored. Finally, near-infrared fluorescence imaging system was used to verify the thrombus-targeting effect of PLT-r-SAK. Results PLT-r-SAK was firstly constructed, which exhibited a uniformly dispersed spherical morphology with a diameter of 185.8 ± 1.5 nm and a zeta potential of -26.1 ± 0.8 mV. In the in-vitro animal experiment, the thrombolysis rate of PLT-r-SAK was significantly higher than that of the same (low) dose and 4-fold (high) dose r-SAK (Figure 1a, 1b). In the in-vivo experiment, the initial recanalization time of PLT-r-SAK was significantly shorter than that of the low dose and high dose r-SAK, and the duration of the reperfusion time of PLT-r-SAK was prolonged compared to low dose and high dose r-SAK (Figure 1c). Another in-vitro experiment showed that the increased thrombolysis rate of PLT-r-SAK could be inhibited by platelet poor plasma (PPP) from aspirin- and ticagrelor-treated patients. Finally, both the in-vitro and in-vivo near-infrared fluorescence imaging showed significantly higher radiant efficiency in the PLT-r-SAK group as compared to the NS group (Figure 2). Conclusions Platelet membrane coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the platelet membrane and can be inhibited by aspirin- and ticagrelor-treated plasma.Thrombolytic efficacy of PLT-r-SAKThrombus-targeting evidence of PLT-r-SAK

Alternatives for controlling insect pests in crops of agronomic interest using Bacillus thuringiensis and Brevibacillus laterosporus

The bacteria Bacillus subtilis and Bacillus thuringiensis have been the main target of research for a long time, making it necessary to identify new microorganisms capable of being used and that accompany the rapid development of biotechnology. The work aims to evaluate the efficiency of isolates of B. thuringiensis and B. laterosporus in controlling caterpillars in crops of agronomic interest. Experiments were conducted with the cultivation of Cotton, Sugarcane, Citrus, Bean, Cabbage, Maize, Soybean and Wheat in different environments to evaluate the efficiency of B. thuringiensis and B. laterosporus isolates in controlling caterpillars. Analysis of variance took place at 5% probability using the F test. Subsequently, the Scott-Knott grouping of means was used at 5% probability. The synergistic use of chemical and biological insecticides promotes satisfactory rates of pest control in crops of agronomic interest. Isolates of B. thuringiensis and B. laterosporus are efficient in controlling caterpillars when applied at the highest dosages tested.

LncPepAtlas: a comprehensive resource for exploring the translational landscape of long non-coding RNAs.

Long non-coding RNAs were commonly viewed as non-coding elements. However, they are increasingly recognized for their ability to be translated into proteins, thereby playing a significant role in various cellular processes and diseases. With developments in biotechnology and computational algorithms, a range of novel approaches are being applied to investigate the translation of long non-coding RNA (lncRNAs). Herein, we developed the LncPepAtlas database (http://www.cnitbiotool.net/LncPepAtlas/), which aims to compile multiple evidences for the translation of lncRNAs and annotations for the upstream regulation of lncRNAs across various species. LncPepAtlas integrated compelling evidence from nine distinct sources for the translation of lncRNAs. These include a dataset comprising 2631 publicly available Ribo-seq samples from nine species, which has been collected and analysed. LncPepAtlas offers extensive annotation for lncRNA upstream regulation and expression profiles across various cancers, tissues or cell lines at transcriptional and translational levels. Importantly, it enables novel antigen predictions for lncRNA-encoded peptides. By identifying numerous peptide candidates that could potentially bind to major histocompatibility complex class I and II molecules, this work may provide new insights into cancer immunotherapy. The function of peptides were inferred by aligning them with experimentally detected proteins. LncPepAtlas aims to become a convenient resource for exploring translatable lncRNAs.

Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity.

The recent unprecedented progress in ageing research and drug discovery brings together fundamental research and clinical applications to advance the goal of promoting healthy longevity in the human population. We, from the gathering at the Aging Research and Drug Discovery Meeting in 2023, summarised the latest developments in healthspan biotechnology, with a particular emphasis on artificial intelligence (AI), biomarkers and clocks, geroscience, and clinical trials and interventions for healthy longevity. Moreover, we provide an overview of academic research and the biotech industry focused on targeting ageing as the root of age-related diseases to combat multimorbidity and extend healthspan. We propose that the integration of generative AI, cutting-edge biological technology, and longevity medicine is essential for extending the productive and healthy human lifespan.

A Simple Analysis of the Second (Extra) Disulfide Bridge of VHHs.

Camelids produce a special type of antibody, known as VHHs, that has lost the VL domain, providing a more optimised VH domain. This particular highly stable antibody domain has interesting properties for biotechnological development. Ordinarily, those molecules possess only one disulphide bridge, but surprisingly, at least a quarter of these VHHs have a second one. Curiously, this does not seem to be essential for the stability and the function of this domain. In an attempt to characterise precisely the role and impact of this disulphide bridge at the molecular level, several in silico mutants of a VHH were created to disrupt this second disulphide bridge and those systems were submitted to molecular dynamics simulation. The loss of the second disulphide bridge leads to an increase in the flexibility of CDR1 and CDR3 and an unexpected rigidification of CDR2. Local conformational analysis shows local differences in the observed protein conformations. However, in fact, there is no exploration of new conformations but a change in the equilibrium between the different observed conformations. This explains why the interaction of VHHs is not really affected by the presence or absence of this second bridge, but their rigidity is slightly reduced. Therefore, the additional disulphide bridge does not seem to be an essential part of VHHs function.

Isolation of Bacillus altitudinis 5-DSW with Protease Activity from Deep-Sea Mineral Water and Preparation of Functional Active Peptide Fractions from Chia Seeds.

In this study, we successfully isolated Bacillus strains with high protease activity from deep-sea mineral water in Korea and used them to obtain functional peptide fractions from chia seeds. The obtained Bacillus strains showed a high similarity of 99% with B. altitude with a long rod type (named B. altitudinis 5-DSW) and high protease activity at 40 °C, and 70% of the activity remained even at 70 °C. The defatted chia seed protein (15-50 kDa) was treated with crude protease from B. altitudinis 5-DSW and digested into small peptides below 20 kDa. The obtained chia seed peptides showed 3 times and 1.5 times higher antioxidant activity in DPPH and ABT radical scavenging assays, respectively. Moreover, chia seed peptides showed enhanced AChE inhibitory activity with an IC50 value of 14.48 ± 0.88 μg/mL and BChE inhibition activity with an IC50 value of 10.90 ± 0.80 μg/mL. Our results indicate that the newly isolated B. altitudinis 5-DSW and chia seed protein hydrolysates have potential applications in biotechnology and functional food development, enhancing the nutritional quality and value-added utilization of chia byproducts.

Contesting the Prescriptibility of Emotion through Affective Encounters in Lucy Prebble’s The Effect (2012)

This paper explores how Lucy Prebble’s The Effect (2012) dramatises the subversive potentialities of affective encounters as an antidote to the isolating, profit-minded forms of posthumanisation prescribed by modern psychiatry. It argues that the play poignantly unveils how the convergence of the psychopharmaceutical industry with advanced capitalism and neoliberal ideology shape popular discourse around mental illnesses and the necessity of medically induced (self-)regulation of emotion. It also investigates how Prebble mingles crisis with hope in the piece by portraying the autonomy and unpredictability of affective bodily responses, which evade being translated into bio-data and destabilise biopsychiatry’s totalizing view of emotions as utterly controllable through the brain. My analysis utilises Rosi Braidotti’s theorisation of the posthuman subject as both susceptible to exploitation and control and as the site of resistance and ongoing transformation, as presented in her work The Posthuman (2013). It also employs Stefan Herbechter’s theories, as expressed in his book Posthumanism: A Critical Analysis (2013), on how biotechnological developments, advanced capitalism and ideology converge, facilitating new forms of self-governmentality. Finally, it refers to Brian Massumi’s conceptualisation of affect, prevalent in his work “The Autonomy of Affect” (1995) as an intense autonomic bodily response which resists processes of control and manipulation. Ultimately, I argue that The Effect highlights the transformative potential of affective encounters and interconnectedness, functioning as resistance to modern psychiatry’s isolating prescription of emotional self-governance through self-medication.

Bioactive compounds from food-grade Bacillus.

Bacillus species have attracted significant attention in recent years due to their potential for producing various bioactive compounds with diverse functional properties. This review highlights bioactive substances from food-grade Bacillus strains and their applications in functional foods and nutraceuticals. The metabolic capacities of Bacillus species have allowed them to generate a wide range of bioactive substances, including vitamins, enzymes, anti-microbial peptides, and other non-ribosomal peptides. These substances have a variety of positive effects, including potential cholesterol-lowering and immune-modulatory qualities in addition to anti-oxidant and anti-bacterial actions. The uses and mechanisms of action of these bioactive chemicals can be used to improve the functional qualities and nutritional profile of food products. Examples include the use of anti-microbial peptides to increase safety and shelf life, as well as the use of Bacillus-derived enzymes in food processing to improve digestibility and sensory qualities. The exploitation of bioactive compounds from food-grade Bacillus strains presents a promising frontier in the development of functional foods and nutraceuticals with enhanced health benefits. Due to their wide range of activity and applications, they are considered as important resources for the development of novel medications, agricultural biocontrol agents, and industrial enzymes. Ongoing research into the biosynthetic pathways, functional properties, and applications of these compounds is essential to fully realize their potential in the food industry. This review underscores the significance of various bioactive compounds generated from Bacillus in tackling global issues like environmental sustainability, sustainable agriculture, and antibiotic resistance. Future developments in microbiology and biotechnology will enable us to fully utilize the potential of these amazing microbes, resulting in novel approaches to industry, agriculture, and health. © 2024 Society of Chemical Industry.

Право человеческого эмбриона и плода на биобезопасность: актуальные вопросы правопонимания и правового регулирования

The article examines topical issues of legal understanding and legal regulation of the right of the human embryo and fetus to biosafety. The idea of forming the legal status of the human embryo and fetus is put forward, similar to the status of a born child with fundamental rights to life, health, dignity and biosafety. The assessment of the established legal approaches to solving such problems as the legal nature of the human embryo and fetus, their right to protection of their natural biological existence and development; protecting embryos and fetuses from abuse of biotechnology and genetic engineering. The author considers it important in the modern legal regulation of the use of biotechnologies to find a balance between rationality and humanism, which allows treating the embryo and fetus as a person, in respect of which an appropriate system of legal protection is being built against modern biological threats and challenges caused, among other things, by the unregulated development of biotechnologies.

APPLICATION OF THE CLASSIFICATION OF TYPES OF THINGS TO HUMAN ORGANS AND TISSUES

With the development of biotechnology, the possibility of human organs and tissues acting as objects of various legal relations becomes obvious: compensated or gratuitous alienation, exchange, etc. However, at present there is no single position regarding the legal nature of human biomaterials. The most popular solution is to recognize organs and tissues as things limited in circulation. However, it is possible to note the lack of sufficient argumentation of the grounds for limiting circulation and the list of types of things to which biomaterials belong. As a result, it is impossible to determine the characteristics of body parts as objects and to form their legal regime. The published work provides a detailed analysis of various approaches to the features of things, created through the study of the works of scientists on this issue using various methods of scientific knowledge (analysis, synthesis, induction, deduction, comparative legal and others). As a result, the author's approach to the features of divisible, indivisible, individually defined, consumable, non-consumable, withdrawn and limited in circulation things is formed. Further, based on the examination of the presence of characteristics in organs and tissues, their classification as divisible or indivisible (depending on the type), unique and individually defined, consumable or non-consumable (depending on the method of use) and limited in circulation items is argued.