In the realm of outdoor furniture, the choice of material plays a crucial role in determining not only the aesthetics but also the longevity of your investment. When it comes to the perfect blend of durability, style, and versatility, a round aluminum outdoor dining set emerges as a top contender. Let’s delve into the reasons why aluminum outdoor furniture, particularly in a round dining set, can transform your outdoor space.

Sleek Elegance with a Round Design

The circular silhouette of a round aluminum outdoor dining set brings a touch of timeless elegance to your patio or garden. The absence of sharp corners not only adds a sense of fluidity to the space but also encourages a more intimate dining atmosphere. The sleek lines of aluminum enhance the overall aesthetics, creating a modern and sophisticated look that seamlessly integrates with various outdoor settings.

Durability in Every Curve

One of the standout features of aluminum outdoor furniture is its inherent durability. Aluminum is naturally resistant to rust and corrosion, ensuring that your outdoor dining set withstands the test of time. The robust nature of this material allows for worry-free placement in different weather conditions, from scorching summer days to rainy seasons. Say goodbye to concerns about deterioration – a round aluminum dining set is built to endure.

Versatility in Style and Placement

Aluminum’s malleability allows for intricate and diverse designs, making it an incredibly versatile material for outdoor furniture. A round dining set crafted from aluminum can be found in a range of styles, from classic to contemporary. Whether your outdoor space leans towards a casual, laid-back vibe or a more formal setting, there’s a round aluminum dining set to suit your taste. Additionally, the lightweight nature of aluminum makes it easy to rearrange and reconfigure your outdoor space whenever inspiration strikes.

Easy Maintenance for Effortless Enjoyment

In the hustle and bustle of modern life, the last thing you want to worry about is extensive furniture maintenance. With a round aluminum outdoor dining set, upkeep is a breeze. A quick wipe with a mild detergent and water is usually all that’s needed to keep your furniture looking as good as new. This low-maintenance feature allows you to focus on enjoying your outdoor space without the hassle of constant care.

The Perfect Centerpiece for Gatherings

Imagine the joy of hosting friends and family around a beautifully crafted round aluminum dining set. The circular layout encourages conversation, creating a warm and inviting atmosphere. Whether it’s a cozy family dinner or a lively gathering with friends, this dining set becomes the perfect centerpiece for memorable moments.

In conclusion, a round aluminum outdoor dining set brings together style, durability, and practicality in one harmonious ensemble. Elevate your outdoor dining experience with a touch of elegance and invest in furniture that not only enhances your space but also stands the test of time.

If you’re ready to transform your outdoor area into a stylish and inviting haven, consider the enduring appeal of a round aluminum outdoor dining set. It’s more than furniture; it’s an investment in years of outdoor enjoyment.

There’s something undeniably alluring about dining under the open sky. The harmony of nature and the joy of sharing a meal with loved ones amidst the fresh air have made outdoor dining a cherished experience. Elevating this experience to a new echelon of sophistication are modern outdoor dining sets that redefine style, comfort, and functionality.

• A Fusion of Form and Functionality:
  Modern outdoor dining sets represent a seamless blend of form and functionality. These sets are meticulously crafted to enhance the aesthetics of your outdoor space while ensuring exceptional comfort and practicality.
• Design Elements that Dazzle:
  At the heart of modern outdoor dining sets lies a captivating design ethos. Clean lines, minimalist silhouettes, and contemporary aesthetics define these sets. The marriage of sleek metal frames, lustrous wood, or resilient synthetic materials creates an ambiance that exudes refined elegance.
• Comfort Amplified:
  Outdoor dining no longer means sacrificing comfort. Modern dining sets prioritize plush cushions, ergonomic designs, and thoughtful seating arrangements. These elements elevate your alfresco dining experience, providing a luxurious yet relaxed atmosphere.
• Material Mastery:
  Materials used in crafting modern outdoor dining sets play a pivotal role in their allure. From weather-resistant aluminum to durable teak and innovative synthetic wicker, these materials ensure longevity, easy maintenance, and resistance to the elements.
• Tailoring Sets to Space:
  Versatility is the hallmark of contemporary outdoor dining sets. Available in a myriad of sizes and configurations, they cater to diverse spaces – be it a sprawling patio, a cozy balcony, or a verdant garden. This adaptability allows you to curate the perfect setting for your outdoor indulgences.
• Elevating the Outdoor Experience:
  Imagine hosting a soirée surrounded by the beauty of nature, with a modern dining set as the centerpiece. The sophistication of these sets enhances the ambiance, transforming any outdoor gathering into an extraordinary affair filled with style and comfort.
• Effortless Maintenance:
  The appeal of modern outdoor dining sets extends beyond their aesthetics. Engineered for durability and resilience, these sets require minimal upkeep. They stand firm against the vagaries of weather, granting you more time to relish outdoor moments without worrying about maintenance.
• Choosing Your Ideal Set:
  Selecting the perfect modern outdoor dining set involves considering factors like space constraints, seating capacity, and personal style preferences. Whether it’s a sleek bistro set or an expansive dining ensemble, there’s a set tailored to suit your needs.
• In Conclusion:
  Al fresco dining reaches new heights of sophistication with the introduction of modern outdoor dining sets. These sets redefine outdoor luxury, creating spaces that radiate elegance and comfort, inviting you to savor every moment spent in the embrace of nature.

Embrace the essence of outdoor elegance and redefine your dining experience. Elevate your al fresco gatherings with the transformative power of modern outdoor dining sets that beautifully blend style, comfort, and functionality.

Outdoor metal furniture refers to furniture pieces designed specifically for outdoor use and constructed primarily from metal materials such as aluminum, steel, or wrought iron. These furnishings are well-suited for outdoor environments due to their durability, weather resistance, and stylish aesthetics. Outdoor metal furniture is a durable and stylish choice for furnishing outdoor spaces. Its resilience against the elements and design flexibility make it a popular option for those seeking long-lasting and aesthetically pleasing outdoor seating and dining solutions. so How to choose the right outdoor metal furniture for yourself?

1. Materials

Let’s first understand 3 common types of outdoor metal furniture: Aluminum Outdoor Furniture, Steel Outdoor Furniture, and Wrought Iron Outdoor Furniture.

1) Aluminum Outdoor Furniture

Aluminum outdoor furniture is a popular choice for outdoor spaces due to its lightweight, corrosion-resistant properties, and contemporary aesthetics. This type of furniture is constructed primarily from aluminum, making it easy to move around and rearrange as needed. Aluminum is naturally rust-resistant, ensuring the furniture’s durability in various weather conditions.

One of the key advantages of aluminum outdoor furniture is its low maintenance requirements. Its resistance to rust means you don’t need to worry about applying special coatings or treatments. Additionally, aluminum furniture often features sleek and modern designs, making it a stylish addition to any outdoor setting, from patios and decks to gardens and poolside areas.

2) Steel Outdoor Furniture

Steel outdoor furniture is a sturdy and robust option for furnishing your outdoor spaces. This type of furniture is crafted primarily from steel, which lends it exceptional durability and strength. Steel outdoor furniture is known for its ability to withstand the rigors of outdoor use, making it a reliable choice for various climates and settings.

One of the standout features of steel outdoor furniture is its longevity. It is highly resistant to wear and tear, making it suitable for areas with heavy foot traffic or exposure to the elements. However, it’s important to note that steel is prone to rust if not properly maintained. To mitigate this, many steel outdoor furniture pieces come with protective coatings or powder-coated finishes, which enhance their resistance to corrosion.

3) Wrought Iron Outdoor Furniture

Wrought iron outdoor furniture is a classic and elegant choice for enhancing the beauty and charm of your outdoor living spaces. This type of furniture is meticulously crafted from wrought iron, which is known for its exceptional strength, durability, and intricate designs. Wrought iron furniture has been a favorite among homeowners for centuries due to its timeless appeal.

One of the defining characteristics of wrought iron outdoor furniture is its ornate and artistic designs. Craftsmen often use this malleable material to create intricate patterns and decorative details, making each piece a work of art. These designs can range from simple and traditional to elaborate and elaborate, allowing you to find a style that matches your outdoor aesthetic.

Selecting the appropriate metal material is a crucial step, and now we will compare the differences between various materials.

Aluminum vs. Steel vs. Wrought Iron Outdoor Furniture

Aspect	Aluminum	Steel	Wrought Iron
Durability	Highly durable; resists corrosion	Durable but can rust if not coated	Exceptionally durable; resists rust
Weight	Lightweight, easy to move	Heavier than aluminum	Heavier than aluminum, lighter than steel
Maintenance	Low maintenance, no rust	Requires regular maintenance	Requires occasional maintenance
Weather Resistance	Excellent, doesn’t corrode	Prone to rust without coating	Resistant to rust, but can chip paint
Price	Moderate to high	Moderate	Moderate to high
Style Options	Wide range of modern designs	Contemporary to traditional styles	Classic and ornate designs
Portability	Easy to move and transport	Moderately easy to move	Moderately easy to move
Customization Options	Limited customizability	Moderate customizability	Highly customizable
Comfort	May require cushions for comfort	Cushions can enhance comfort	Cushions can enhance comfort

 

Summary:

 

• Aluminum: Offers excellent durability and low maintenance but may require cushions for added comfort. It is lightweight and suitable for modern designs.
• Steel: Moderately durable, moderately priced, and requires regular maintenance to prevent rust. It offers a range of contemporary to traditional styles.
• Wrought Iron: Exceptionally durable and resistant to rust, but it may require occasional maintenance. Known for classic and ornate designs, highly customizable and moderately priced.

In addition to materials, we also need to consider factors such as durability, style, size, budget, after-sales service, and more.

2. Durability

Durability is indeed crucial for outdoor furniture due to exposure to various weather conditions. Seeking furniture with coatings or treatments that resist rust and corrosion is important. Powder-coated finishes are known for their high durability. Nowadays, almost all metal furniture on the market features powder-coated finishes, effectively extending the lifespan of outdoor furniture. Even if the paint starts to peel off, it can still be repaired by oneself.

3. Style and Aesthetics

When choosing metal furnishings for your outdoor area, it’s crucial to consider the overarching style and visual appeal. Metal furniture comes in a diverse array of designs, spanning from contemporary to timeless classics. Typical color options for metal furniture include black, gray, and white. Black metal furniture imparts an air of mystery and nobility, while gray metal furniture exudes understated elegance. White, on the other hand, evokes a sense of cleanliness and purity. Opt for a design that seamlessly blends with your outdoor decor and enhances the overall atmosphere of the environment.

4. Comfort

Comfort is paramount. Evaluate the seating and, if applicable, the cushions. Ensure that the furniture provides a comfortable seating experience, even for extended periods. Whether you are considering metal outdoor furniture, wicker, or any other material, cushions can significantly enhance comfort. Additionally, carefully consider the material of the cushions. It is advisable to choose cushions that are waterproof, resistant to moisture, and capable of preventing mildew growth, among other factors.

5. Maintenance

Consider your willingness to invest in maintenance. Certain metal furniture options may necessitate regular cleaning and upkeep to maintain their optimal appearance. Among outdoor furniture choices, metal furniture generally demands the least maintenance, with aluminum furniture standing out as an excellent option. Aluminum is inherently resistant to corrosion, rust, and wear, making it a top choice for outdoor furniture. Furthermore, its lightweight nature makes it the preferred selection for outdoor furnishing.

6. Size and Space

Take accurate measurements of your outdoor space to ensure that the furniture fits comfortably. Avoid overcrowding the area, leaving ample room for ease of movement. It would be disappointing to purchase outdoor furniture that you adore only to discover it doesn’t fit in your intended space. Therefore, be diligent in verifying the dimensions before making your purchase. You can typically find comprehensive product information on the product details page or seek assistance from customer service if needed.

7. Budget & Warranty

Establish a budget for your outdoor furniture purchase. Metal outdoor furniture is available in a wide range of price points, so it’s crucial to determine your spending limit. Affordable options can be found in the 200-500 dollar range, while more luxurious pieces can run into the thousands of dollars. Prioritize finding options that offer both affordability and quality. If you are willing to invest more, consider exploring Jardina: mordern style, a brand known for its quality and backed by a 2-year warranty. Keep in mind that some extremely low-priced brands may lack reliable after-sales service in case of issues. Remember, while price is important, it should not be the sole factor guiding your decision-making process.

8. Local Climate

Consider the impact of your local climate. The weather conditions in your area will influence your choice of outdoor furniture. If you reside in a region characterized by severe weather, it’s advisable to opt for furniture that is exceptionally durable and weather-resistant. For coastal areas, wood furniture may not be the best choice due to its vulnerability to saltwater exposure, while in consistently rainy climates, furniture crafted from rattan materials may not fare well.

 

Selecting outdoor metal furniture may initially appear challenging, but it’s a straightforward process with the convenience of online shopping. All you need to do is allocate some time for browsing and exploration, and you’re sure to discover the perfect product that suits your preferences. Here’s to everyone enjoying a fantastic outdoor lifestyle!

Cytokine division belongs to Creative Proteomics, which specializes in providing cytokine research and analysis services for researchers in the pharmaceutical and biotechnology industries, as well as academic institutes and government agencies. Creative proteomics recently announced high sensitivity and wide detection range quantitative detection for systemic lupus erythematosus related cytokines and proteins through a variety of technologies.

 

Systemic lupus erythematosus is a typical systemic autoimmune disease characterized by the loss of autoimmune tolerance and the production of high levels of autoreactive antibodies against autoantigens, which leads to organ damage. This process involves a variety of cytokines. In human and mouse model systems, long-term expression of CD40L in lupus T cells may lead to excessive B cell activation, which in turn leads to the pathogenesis of the disease.

 

Creative Proteomics’s Luminex cytokine detection platform can detect the following cytokines involved in systemic lupus erythematosus:

• IL-6, IL-10, IL-12, IL-18, IFN-γ all suggest that the expression level of SLE will change to varying degrees during the development of SLE. IFN-γ inhibits the differentiation of Th0 to Th2. IL-4 and IL-10 inhibit the differentiation of Th0 to Th1. Cytokines secreted by mononuclear macrophages such as IL-12 and IL-18 also have a regulatory effect on Th1/Th2 differentiation.

 

• The B lymphocyte stimulation (BLyS) factor is a new member of the TNF ligand superfamily. It has strong proliferation, differentiation and antibody secretion effects on B cells, and plays an important role in the pathological process of SLE. TGF-β expression levels in SLE patients’ serum and urine are abnormal, suggesting that it could be a potential therapeutic target.

 

• TNF-α is a multifunctional pleiotropic cytokine in the immune system. It can not only promote the development of autoimmune inflammation, but also slow down the process of inflammation. It is an effective therapeutic target. For the treatment of SLE, a number of therapeutic TNF-α inhibitors have been developed.

 

“We mainly use the Luminex cytokine detection platform, which uses fluorescently encoded microspheres with specific antibodies to different target molecules. The different microspheres can be combined freely to a certain extent, so that up to 100 analytes can be tested multiple times simultaneously in a single experiment,” stated Creative Proteomics’s Product Manager.

 

“Creative Proteomics also uses flow cytometry (FACS analysis) and enzyme-linked immunosorbent assay (ELISA) to perform simultaneous quantitative detection of cytokines related to systemic lupus erythematosus disease with higher sensitivity and a wider detection range,” he added.

 

About Creative Proteomics

Creative Proteomics is an innovative contract research organization that focuses on using advanced equipment platforms and optimized detection technology to help researchers around the world reduce time and costs. The company has a proprietary laboratory information management system to strengthen laboratory quality monitoring and quality management to ensure the efficiency and security of customer data.

Introduction to CRISPR Screen Sequencing

CRISPR Screen technology is used for high-throughput screening, allowing a large number of gene mutant cells to be created and a mutant cell library to be screened in various external environments. The relationship between phenotype and genotype can be further evaluated using high-throughput sequencing and bioinformatics analysis. Furthermore, high-throughput screening based on the CRISPR/Cas9 library overcomes the limitations of RNA interference screening technology, such as low transfection efficiency and the capacity to repress gene expression only at the mRNA level. In the era of precision medicine, it has a lot of scientific research value and a lot of application space.

 

The CRISPR Screen is a high-throughput molecular target screening method. A successful CRISPR Screen begins with a well-designed sgRNA library that targets the desired genes or loci. sgRNA is designed based on sequence, then synthesized, then cloned to vector or transcribed into RNA for cell transfection. Then, using commonly used positive or negative selection, run a screen. Following the physical separation of cells into two or more populations, PCR amplification and massively parallel sequencing will be carried out. The sgRNA and targeted genes of concern will be detected after data analysis.

 

Types of CRISPR Screen

There are several types of CRISPR screen which includes the following

1. CRISPR KO screening with complete loss of gene expression allows for the largest phenotypic effect window and the highest statistical power for hit discovery.
2. CRISPRi screening suppresses expression rather than completely knocking out the target gene, making it ideal for studying druggability and assessing the function of genes that are essential or amplified when knocked out.
3. CRISPRa screening amplifies gene expression in its natural setting, allowing researchers to study activation-related responses on a genome-wide scale for the first time.

 

Workflow of Wide CRISPR/Cas9 Knockout Screening and Sequencing

1. sgRNA Library Development sgRNAs are constructed computationally, synthesized, PCR amplified, and cloned into a vector delivery system.
2. Screening Inject cells with sgRNA, Cas9, and other required components. After that, the desired clones are chosen, and DNA is extracted.
3. Sequencing PCR and next-generation sequencing
4. Analysis and measurement sgRNAs are restored, evaluated, and associated genes are discovered.

 

Applications of CRISPR Screening and Sequencing

Some of the applications of CRISPR screening and sequencing are the following

1. To find disease-related genes Genome-wide CRISPR/Cas9 screening can be utilized to explore disease-related genes, which is critical for the discovery of new drug targets and treatment strategies.
2. To research non-coding DNA sequences Non-coding RNA, cis- and trans-regulatory elements, introns, pseudogenes, telomeres, repetitive sequences, and other non-coding DNA sequences make up about 98 percent of the human genome sequence.
3. To investigate regulatory networks Genome-wide screening with CRISPR/Cas9 has been widely used in various fields of cell biology. However, phenotyping is mostly used in cell proliferation, viability, drug resistance, and reporter gene expression, among other things. Within cells, more complex biological regulatory networks (such as the transcriptome and gene interaction) require further investigation.

 

About CD Genomics

CD Genomics provides the research community with high-quality next-generation sequencing, third-generation sequencing, genotyping, microarray, and population genetics services. CD Genomics has become an influential company in the industry and continues to innovate, keeping up with the forefront of scientific research and leading the latest and most comprehensive genomics technical support.

 

CD Genomics has harnessed amplicon-based next-generation sequencing to create an inexpensive, reliable, and high-throughput strategy for CRISPR Screen sequencing to meet the emerging needs of research communities CRISPR Screen sequencing service can provide direct and precise data about sgRNA and targeted gene analysis and functional enrichment analysis, to assist researchers to study genes functions in a high-throughput fashion.

Bioinformatics-analysis Platform belongs to CD Genomics, which provides reliable next-generation and third-generation high-throughput sequencing data analysis, comprehensive technology services, database construction, and other related data analysis business. The platform is a leading open solution for data-driven innovation, which aims to discover the hidden potential in biological data and unearth new insights or predict new prospects related to life science research. CD Genomics has recently announced Epigenetics Data Analysis to move your disease research forward.

 

Gene regulation of diseases and pathogenesis is usually affected by epigenetic characteristics such as DNA methylation, chromatin structure, and non-coding RNA (ncRNA). These characteristics are part of complex control loops and require reliable research tools. CD Genomics has developed powerful epigenetic research and analysis technologies covering sample preparation, sequencing, quantitative PCR, functional analysis experiments, and bioinformatics tools.

 

Epigenetic modifications are reversible modifications that affect gene expression without changing the DNA sequence, and can be inherited during cell division. DNA methylation is the most characterized modification. Epigenetic modification plays an important role in gene expression and regulation, and participates in many cellular processes, such as differentiation, development, and tumorigenesis.

 

DNA methylation is most common in the C5 position of cytosine, followed by guanine (CpG site) in vertebrates, or non-CpG sites in plant or mammalian embryonic stem cells, such as CHG and CHH. DNA methylation is established and maintained by DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b). CD Genomics uses a mature high-throughput sequencing platform combined with epigenetics to provide a variety of biological information analysis services such as genome-wide epigenetic location analysis and gene expression regulation mechanism research.

 

“Currently, epigenetic bioinformatics analysis focuses on DNA methylation and histone modification. Mining key information from epigenetic sequencing data through bioinformatics is the foundation of epigenetic research,” said Chief Scientist at CD Genomics.

 

“CD Genomics’s analysis team not only provides standardized biological information analysis content, but also provides personalized customized analysis services according to customer project requirements. If you are looking for epigenetic sequencing data analysis, we will develop corresponding analysis strategies accordingly,” he added.

 

About CD Genomics

CD Genomics is one of the global bioinformatics analysis service providers, which based on the high-performance computing platform and the bioinformatics analysis team dominated by Ph.D. and Master. CD Genomics uses cutting-edge bioinformatics analysis technology to carry out the main business of genomics, transcriptomics, microorganisms, epigenetics, proteomics, metabolomics, single-cell omics and so on.

BOC Sciences has put its back into chemical and biochemical production for years while it also focuses on cutting-edge research in these fields. Lately, it projects a webinar themed as Targeting RNA Structure as a Therapeutic Strategy, awaiting broad participation on January 19th, 2022.

 

As a leading chemical and biochemical supplier, BOC Sciences seeks to strengthen communication in the research field, notably about frontier breakthroughs. Hence, BOC Sciences invites Silvia Rouskin, an assistant professor of Harvard Medical School, to present her latest research about the RNA genome that forms alternative conformations in cells. Additionally, the therapeutic strategies of targeting RNA structures, as well as their applications in drug development are covered in the webinar.

 

Silvia Rouskin did her Ph.D. in Jonathan Weissman’s lab at UCSF and then specialized in RNA structure research. To conquer the weaknesses of traditional methods for characterizing RNA structures, either merely determining the average structure or failing to be applied inside cells, Dr. Rouskin and her fellows developed the DREEM algorithm to deconvolute single-molecule chemical probing data (DMS-MaPseq) for identifying the ensembles of alternative RNA structures inside living cells.

 

Basic information about the webinar:

Subject: Targeting RNA Structure as a Therapeutic Strategy

Speaker: Silvia Rouskin

Time: January 19th, 2022 14:00 EST | January 19th, 2022 22:00 CET

Highlights:

* Determine RNA Structure in Cells

* Quantify Alternative Conformations

* Target RNA Structure

Register at: https://www.bocsci.com/targeting-rna-structure-as-a-therapeutic-strategy.html.

 

Besides the dedication to academic communications, BOC Sciences also plows in the chemical raw material industry. It has yielded a complete set of high-quality chemical products contributing to all phases of drug discovery. It is worth noting that pseudoUridines, the most abundant RNA modification in cellular RNA, are in adequate supply at BOC Sciences. Its yearly output of pseudoUridine and its derivatives has exceeded 500kg, which can satisfy both research and production requirements.

 

Predictably, accompanied by experienced experts and first-class techniques, BOC Sciences will enlarge both production capacity and product categories of pseudoUridines in the following years.

 

About

BOC Sciences is a renowned chemical and biochemical supplier serving plenty of academic institutions or industrial manufacturers. Owing to the unceasing optimization for products and services, BOC Sciences is evaluated as a trustworthy cooperative partner, encouraging it to make further progress in the profession. Moreover, BOC Sciences plans to organize a series of webinars concerning the most forward research findings, hopefully, which will witness some favorable changes in the whole industry.

There are docking stations called receptors on the surface of our cells. Various compounds ranging from caffeine and dopamine to heroin, tetrahydrocannabinol (THC) and lysergic diethylamine (LSD) all bind to these receptors. Indeed, G protein-coupled receptors are the intended target of action for more than 30% of drugs currently on the market. But these drugs often also target unintended targets — imagine, blanket bombardment of the nervous system, resulting in a long list of side effects often heard at the end of drug advertisements.

 

Dr. Bryan L. Roth, professor of pharmacology at the University of North Carolina School of Medicine in the United States, said, “What we need is more precise, less harmful, and equally effective treatments. But developing these better drugs is not easy. Drug developers need to know the exact chemical structure of the drug and the expected receptor in order to produce the exact chemical reaction we want within the cell. It is most important to ensure that the drug does not affect other receptors or bind to target receptors, but binding in such a way can trigger unexpected consequences in the cell.”

 

“In the past, scientists have tested molecules one by one against therapeutic targets, a long and expensive operation,” Roth said. Therefore, scientists have constructed virtual molecular libraries and complex computer programs to test hundreds of thousands of molecules at a time. What we call ‘testing’ means that a computer program searches a molecular database in which a large number of molecules can theoretically be created and can theoretically bind to a given cellular receptor with appropriate affinity. Scientists can then adjust chemical bonds in a computer program to optimize the structure of the molecule. Scientists can then actually make a small fraction of these molecules and test them in cell cultures.”

 

The establishment of virtual libraries is a great leap forward in the field. Testing hundreds of thousands of possible molecules sounds like many, and some of them may have properties worth studying. However, there are billions of possible chemical combinations that could theoretically lead to the creation of nearly infinite molecules or potential drugs. As a result, scientists eventually create huge libraries of theoretical compounds: billions of mostly ‘undiscovered’ and unexplored molecules, which may or may not bind to specific cellular targets; they may or may not have therapeutic value at all.

 

“Unfortunately, the chemical space is huge,” says Roth. “It is estimated that there are more chemical species in theory than there are actually molecules in the universe. Only a small fraction of potential chemicals can be physically tested.”

 

Therefore, in a new study, Roth collaborated with researchers from the University of Southern California and Tohoku University to validate V-SYNTHES, a novel computational method developed by Dr. Vsevolod Katritch at the University of Southern California, allowing scientists to first determine the optimal combination of building blocks called synthon—intramolecular hypothetical units. As a seed, synthon can grow into a molecular hierarchy with the best predictive power for binding to receptor targets. The findings were published online in the Nature under the title “Synthon-based ligand discovery in virtual libraries of over 11 billion compounds”.

 

“This approach allows scientists to test billions of compounds against a therapeutic target by computational methods,” Roth said. “To our knowledge, the largest successful computational screening to date. ”

 

As described in the paper, these authors tested 11 billion theoretical compounds against the cannabinoid receptor CB2, which is targeted by THC, the active ingredient of cannabis.

 

The Katritch laboratory developed this method and performed computational studies. With the help of Dr. Alexandros Makryannis’s laboratory and Roth’s laboratory at Tohoku University, they discovered a new compound, which is a highly selective and potent CB2 antagonist — a compound that inhibits or prevents receptor activity. This screening and discovery were then validated by the Makryannis lab and Roth lab. They further validated this process against another target—the kinase ROCK1.

 

“V-SYNTHES represents a significant advance in the field of drug discovery,” Roth says. It is easily scalable and adaptable, and it should open new perspectives for the discovery of potentially therapeutic chemicals for a large number of diseases, the speed of which was previously impossible to achieve.”

In a new study, researchers from the Princess Margaret Cancer Center of the Canadian University Medical Network and the University of Toronto improved anti-tumor responses by carrying out a series of elegant experiments to construct “super soldiers” with specific leukocytes. Specifically, they describe an epigenetic therapy that modifies DNA and can convert killer T cells into “super soldiers” by enhancing their ability to kill cancer cells. The results were published in Molecular Cell, entitled “DNA hypomethylating agents increase activation and cytolytic activity of CD8 + T cells”. The corresponding author of the paper is Dr. Daniel D. De Carvalho of Princess Margaret Cancer Center. The first author of the paper is Helen Loo Yau, PhD student at Princess Margaret Cancer Center, and Dr. Emma Bell, postdoctoral researcher.

 

Their findings may enhance immunotherapy, a new model of cancer treatment that is currently effective for a small number of cancer patients. Some patients respond well to immunotherapy with dramatic reduction in tumor size, but others respond only partially or not at all. Clinicians and scientists around the world are trying to understand why immunotherapy is only helpful for some patients.

Dr. De Carvalho said, “Our future goal is to use the strategy to combine with other immunotherapies to enhance anti-tumor immunity. We imagine future clinical trials: we collect T cells from patients and perform epigenetic therapy in the laboratory. This may expand the army that kills cancer cells (i.e., cells that kill cancer cells) and effectively construct a ‘super soldier army’. These cells can then be reinjected into the patient, thereby potentially enhancing their intrinsic immune response to the tumor.”

Dr. De Carvalho’s laboratory first observed that T cell infiltration was increased in tumors from mice treated with epigenetic therapy. When they removed these T cells, this therapy no longer worked, suggesting that these T cells played a promoting role in the success of this therapy.

 

These researchers, interested in this finding, set out to apply this epigenetic DNA-modifying therapy directly to T cells in the laboratory. They isolated T cells from healthy human donors as well as patients with melanoma, breast, ovarian, and colorectal cancers. Their results demonstrate that this epigenetic therapy enhances the cancer-killing ability of these T cells.

Epigenetics works by adding or removing chemical “tags” to DNA. Like removable convenience stickers, these labels help specify which genes can be turned on or off. Simply put, you can use drugs that alter these epigenetic signatures to change the function of cells.

In essence, these researchers found that an available chemotherapeutic drug removes specific epigenetic signatures that give way to genes in a proportion of key genes of T cells in a closed state. Removing these tags allows these genes to be returned on and act as a “turbo”, making these T cells a more effective cancer-killing machine.

These researchers discovered two specific genes activated by this epigenetic therapy that are responsible for these T cells becoming better at killing cancer cells.

 

High-dimensional single-cell mass cytometry analysis—a new generation of technology that can dissect single-cell and drug responses—has found that T cells increase the number of granzyme and perforin proteins used to perform killing function. When granzymes and perforin are released, like a fatal special police force, perforin is able to punch holes in the cell membrane and allow granzymes to enter infected cells or cancer cells and complete the task of killing these cells.

Dr. De Carvalho explained, “These T cells become some kind of ‘super soldier’ and carry highly activated molecules, with better weapons, to destroy cancer cells.” The molecular mechanism of how this process occurs is described in detail.

A key innovation in the paper is the use of epigenetic therapy to affect the behavior of genes in T cells. Most studies on epigenetic therapies have focused on their effects on cancer cells. However, the paper focuses on how our immune cells respond, which provides new implications for how we improve the anti-tumor activity of the immune system.

 

This emerging field of epigenetic therapy aims to influence genetic activity without actually modifying the sequence of DNA, thus making it an exciting therapeutic avenue for cancer research.

Dr. De Carvalho said, “It is not experimentally simple to genetically manipulate immune cells for treatment. Its clinical application is more complex and expensive. Our study lays the foundation for clinical research that combines epigenetics with other immunotherapeutic strategies.”

Along with the increasing demand for supportive technologies in novel drug development, Creative Biolabs‘ PROTAC service is accepted by academic or industrial customers worldwide and largely boosts drug research.

 

Proteolysis targeting chimeric molecule (PROTAC) is deemed as an alternative to the traditional molecular drug discovery method since it engages the body’s natural protein disposal system to selectively degrade disease-causing proteins rather than concentrating on controlling protein activity. On account of its broad prospect, Creative Biolabs has been striving to perfect the PROTAC service package for years. Currently, it owns a complete set of technologies including PROTAC design, PROTAC in vitro evaluation, and PROTAC in vivo animal tests.

 

As the very first stage of initiating PROTAC projects, PROTAC design and the corresponding services receive tremendous concerns from technicians of Creative Biolabs. With Continuous efforts, the experienced team has established a PROTAC design service platform including ligand design for target protein, ligand screening for E3 ligase, and linker design and optimization.

 

The present studies reveal that PROTACs with distinct chemical linker types, locations, and lengths have different efficiencies for target protein degradation. Considering the significance of PROTAC linkers, Creative Biolabs allocates great amounts of energy to linker design. Thus far, multiple linkers of Creative Biolabs, such as PEG linker, Alkyl linker, and “click chemistry” linker, have been employed in PROTAC ternary complex formation. Additionally, Creative Biolabs extends its techniques to PROTAC linker optimization through which both the length and position of linkers can be optimized and customized in accordance with distinct requirements.

 

When the PROTAC projects step to the latter stages of development, it is critical to conduct PROTAC in vivo animal tests that can investigate the safety and potential of the drugs. In this field, Creative Biolabs owns a broad collection of test services such as in vivo ADME.

 

ADME studies aim at accurately assessing pharmacokinetics and pharmacology for absorption, distribution, metabolism, and excretion of potential candidate drugs, hence uncovering the possibilities of them being pushed into clinical trials. After the long-term devotion, Creative Biolabs exhibits potent competence to launch varieties of in vivo ADME studies by radio-labeled materials either from clients or synthesized through different administration routes. Moreover, it keeps enriching the in vivo assay platform to contain the maximum scope of animal models and administration routes. “Backed by state-of-the-art techniques and equipment, we have faith in making more contributions to ADME tests and ultimately to lead candidate selection, lead optimization, preclinical testing, and clinical practice,” a senior technician said at Creative Biolabs’ annual meeting.

 

Characteristics of Creative Biolabs‘ PROTAC solutions

• Overall PROTAC services
• Specialized and skillful technical personnel
• Well-equipped facilities and factories
• High efficiency and reliable quality

 

 

About Creative Biolabs

Creative Biolabs is a technical group committed to assisting in novel drug discovery and engineering. Through years of hard work, it has built a comprehensive PROTAC service platform and outshined in the field of biotech. The full services which range from molecule design to evaluation, from off-the-shelf products to individual customization will certainly fit diverse demands for drug discovery and motivate its progress.