Enhancing the stretchability of two-dimensional materials through kirigami: a molecular dynamics study on tungsten disulfide.

In recent years, the 'kirigami' technique has gained significant attention for creating meta-structures and meta-materials with exceptional characteristics, such as unprecedented stretchability. These properties, not typically inherent in the original materials or structures, present new opportunities for applications in stretchable and wearable electronics. However, despite its scientific and practical significance, the application of kirigami patterning on a monolayer of tungsten disulfide (WS2), an emerging two-dimensional (2D) material with exceptional mechanical, electronic, and optical properties, has remained unexplored. This study utilizes molecular dynamics (MD) simulations to investigate the mechanical properties of monolayer WS2 with rectangular kirigami cuts. We find that, under tensile loading, the WS2 based kirigami structure exhibits a notable increase in tensile strain and a decrease in tensile strength, thus demonstrating the effectiveness of the kirigami cutting technique in enhancing the stretchability of monolayer WS2. Additionally, increasing the overlap ratio enhances the stretchability of the structure, allowing for tailored high strength or high strain requirements. Furthermore, our observations reveal that increasing the density of cuts and reducing the length-to-width ratio of the kirigami nanosheet further improve the fracture strain, thereby enhancing the overall stretchability of the proposed kirigami patterned structure of WS2.

Decellularized extracellular matrix-decorated 3D nanofiber scaffolds enhance cellular responses and tissue regeneration.

The use of decellularized extracellular matrix products in tissue regeneration is quite alluring yet practically challenging due to the limitations of its availability, harsh processing techniques, and host rejection. Scaffolds obtained by either incorporating extracellular matrix (ECM) material or coating the surface can resolve these challenges to some extent. However, these scaffolds lack the complex 3D network formed by proteins and growth factors observed in natural ECM. This study introduces an approach utilizing 3D nanofiber scaffolds decorated with dECM to enhance cellular responses and promote tissue regeneration. Notably, the dECM can be customized according to specific cellular requirements, offering a tailored environment for enhanced therapeutic outcomes. Two types of 3D expanded scaffolds, namely radially aligned scaffolds (RAS) and laterally expanded scaffolds (LES) fabricated by the gas-foaming expansion were utilized. To demonstrate the proof-of-concept, human dermal fibroblasts (HDFs) seeded on these scaffolds for up to 8 weeks, resulted in uniform and highly aligned cells which deposited ECM on the scaffolds. These cellular components were then removed from the scaffolds through decellularization (e.g., SDS treatment and freeze-thaw cycles). The dECM-decorated 3D expanded nanofiber scaffolds can direct and support cell alignment and proliferation along the underlying fibers upon recellularization. An in vitro inflammation assay indicates that dECM-decorated LES induces a lower immune response than dECM-decorated RAS. Further, subcutaneous implantation of dECM-decorated RAS and LES shows higher cell infiltration and angiogenesis within 7 and 14 days than RAS and LES without dECM decoration. Taken together, dECM-decorated 3D expanded nanofiber scaffolds hold great potential in tissue regeneration and tissue modeling. STATEMENT OF SIGNIFICANCE: Decellularized ECM scaffolds have attained widespread attention in biomedical applications due to their intricate 3D framework of proteins and growth factors. Mimicking such a complicated architecture is a clinical challenge. In this study, we developed natural ECM-decorated 3D electrospun nanofiber scaffolds with controlled alignments to mimic human tissue. Fibroblasts were cultured on these scaffolds for 8 weeks to deposit natural ECM and decellularized by either freeze-thawing or detergent to obtain decellularized ECM scaffolds. These scaffolds were tested in both in-vitro and in-vivo conditions. They displayed higher cellular attributes with lower immune response making them a good grafting tool in tissue regeneration.

Enhancing the Therapeutic Efficacy of GLP-1 for Hyperglycemia Treatment: Overcoming Barriers of Oral Gene Therapy with Taurocholic Acid-Conjugated Protamine Sulfate and Calcium Phosphate.

Activating the glucagon-like peptide-1 (GLP-1) receptor by oral nucleic acid delivery would be a promising treatment strategy against hyperglycemia due to its various therapeutic actions. However, GLP-1 receptor agonists are effective only in subcutaneous injections because they face multiple barriers due to harsh gastrointestinal tract (GIT) conditions before reaching the site of action. The apical sodium bile acid transporter (ASBT) pathway at the intestinal site could be an attractive target to overcome the problem. Herein, we used our previously established multimodal carrier system utilizing bile salt, protamine sulfate, and calcium phosphate as excipients (PTCA) and the GLP-1 gene as an active ingredient (GENE) to test the effects of different formulation doses against diabetes and obesity. The carrier system demonstrated the ability to protect the GLP-1 model gene encoded within the plasmid at the GIT and transport it via ASBT at the target site. A single oral dose, regardless of quantity, showed the generation of GLP-1 and insulin from the body and maintained the normoglycemic condition by improving insulin sensitivity and blood sugar tolerance for a prolonged period. This oral gene therapy approach shows significantly higher therapeutic efficacy in preclinical studies than currently available US Food and Drug Administration-approved GLP-1 receptor agonists such as semaglutide and liraglutide. Also, a single oral dose of GENE/PTCA is more effective than 20 insulin injections. Our study suggests that oral GENE/PTCA formulation could be a promising alternative to injection-based therapeutics for diabetics, which is effective in long-term treatment and has been found to be highly safe in all aspects of toxicology.

Injectable and rapidly expandable thrombin-decorated cryogels achieve rapid hemostasis and high survival rates in a swine model of lethal junctional hemorrhage.

Effective therapies are urgently needed to stabilize patients with marginally compressible junctional hemorrhage long enough to get them to the hospital alive. Herein, we report injectable and rapidly expandable cryogels consisting of polyacrylamide and thrombin (AT cryogels) created by cryo-polymerization for the efficient management of lethal junctional hemorrhage in swine. The produced cryogels have small pore sizes and highly interconnected porous architecture with robust mechanical strength. The cryogels exhibit rapid shape memory properties and prove to be resilient against fatigue. These cryogels also show high water/blood absorption capacity, fast blood clotting effect, and enhanced adhesion of red blood cells and platelets in vitro. Further, in vivo, hemostatic efficacy tests in a lethal swine junctional hemorrhage model suggest that treatment with AT cryogels, especially AT-2 cryogels, achieves the least blood loss and the highest survival rate (100 %) compared to currently employed products such as XStat® and combat gauze. The high hemostatic performance of the cryogels may be attributed to highly interconnected porous architecture with small pore size and the use of thrombin as a pro-coagulant agent. Collectively, injectable and rapidly expandable thrombin-decorated polyacrylamide-based cryogels show significant promise as hemostatic material, offering effective management of marginally compressible junctional hemorrhages in prehospital settings.

Transforming layered 2D mats into multiphasic 3D nanofiber scaffolds with tailored gradient features for tissue regeneration.

Multiphasic scaffolds with tailored gradient features hold significant promise for tissue regeneration applications. Herein, this work reports the transformation of two-dimensional (2D) layered fiber mats into three dimensional (3D) multiphasic scaffolds using a 'solids-of-revolution' inspired gas-foaming expansion technology. These scaffolds feature precise control over fiber alignment, pore size, and regional structure. Manipulating nanofiber mat layers and Pluronic F127 concentrations allows further customization of pore size and fiber alignment within different scaffold regions. The cellular response to multiphasic scaffolds demonstrates the number of cells migrated and proliferated onto the scaffolds are mainly dependent on the pore size rather than fiber alignment. In vivo subcutaneous implantation of multiphasic scaffolds to rats reveals substantial cell infiltration, neo tissue formation, collagen deposition, and new vessel formation within scaffolds, greatly surpassing the capabilities of traditional nanofiber mats. Histological examination indicates the importance of optimizing pore size and fiber alignment for promotion of cell infiltration and tissue regeneration. Overall, these scaffolds have potential applications in tissue modeling, studying tissue-tissue interactions, interface tissue engineering, and high-throughput screening for optimized tissue regeneration.

Copper-Cystine Biohybrid-Embedded Nanofiber Aerogels Show Antibacterial and Angiogenic Properties.

Copper-cystine-based high aspect ratio structures (CuHARS) possess exceptional physical and chemical properties and exhibit remarkable biodegradability in human physiological conditions. Extensive testing has confirmed the biocompatibility and biodegradability of CuHARS under diverse biological conditions, making them a viable source of essential Cu2+. These ions are vital for catalyzing the production of nitric oxide (NO) from the decomposition of S-nitrosothiols (RSNOs) found in human blood. The ability of CuHARS to act as a Cu2+ donor under specific concentrations has been demonstrated in this study, resulting in the generation of elevated levels of NO. Consequently, this dual function makes CuHARS effective as both a bactericidal agent and a promoter of angiogenesis. In vitro experiments have shown that CuHARS actively promotes the migration and formation of complete lumens by redirecting microvascular endothelial cells. To maximize the benefits of CuHARS, they have been incorporated into biomimetic electrospun poly(ε-caprolactone)/gelatin nanofiber aerogels. Through the regulated release of Cu2+ and NO production, these channeled aerogels not only provide antibacterial support but also promote angiogenesis. Taken together, the inclusion of CuHARS in biomimetic scaffolds could hold great promise in revolutionizing tissue regeneration and wound healing.

Mechanically resilient hybrid aerogels containing fibers of dual-scale sizes and knotty networks for tissue regeneration.

The structure and design flexibility of aerogels make them promising for soft tissue engineering, though they tend to come with brittleness and low elasticity. While increasing crosslinking density may improve mechanics, it also imparts brittleness. In soft tissue engineering, resilience against mechanical loads from mobile tissues is paramount. We report a hybrid aerogel that consists of self-reinforcing networks of micro- and nanofibers. Nanofiber segments physically entangle microfiber pillars, allowing efficient stress distribution through the intertwined fiber networks. We show that optimized hybrid aerogels have high specific tensile moduli (~1961.3 MPa cm3 g-1) and fracture energies (~7448.8 J m-2), while exhibiting super-elastic properties with rapid shape recovery (~1.8 s). We demonstrate that these aerogels induce rapid tissue ingrowth, extracellular matrix deposition, and neovascularization after subcutaneous implants in rats. Furthermore, we can apply them for engineering soft tissues via minimally invasive procedures, and hybrid aerogels can extend their versatility to become magnetically responsive or electrically conductive, enabling pressure sensing and actuation.

Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications.

Nitric oxide (NO) is a gaseous molecule that has a central role in signaling pathways involved in numerous physiological processes (e.g., vasodilation, neurotransmission, inflammation, apoptosis, and tumor growth). Due to its gaseous form, NO has a short half-life, and its physiology role is concentration dependent, often restricting its function to a target site. Providing NO from an external source is beneficial in promoting cellular functions and treatment of different pathological conditions. Hence, the multifaceted role of NO in physiology and pathology has garnered massive interest in developing strategies to deliver exogenous NO for the treatment of various regenerative and biomedical complexities. NO-releasing platforms or donors capable of delivering NO in a controlled and sustained manner to target tissues or organs have advanced in the past few decades. This review article discusses in detail the generation of NO via the enzymatic functions of NO synthase as well as from NO donors and the multiple biological and pathological processes that NO modulates. The methods for incorporating of NO donors into diverse biomaterials including physical, chemical, or supramolecular techniques are summarized. Then, these NO-releasing platforms are highlighted in terms of advancing treatment strategies for various medical problems.

Triggered release of antimicrobial peptide from microneedle patches for treatment of wound biofilms.

Biofilms pose a great challenge for wound management. Herein, this study describes a near-infrared (NIR) light-responsive microneedle patch for on-demand release of antimicrobial peptide for treatment of wound biofilms. IR780 iodide as a photothermal conversion agent and molecularly engineered peptide W379 as an antimicrobial agent are loaded in dissolvable poly(vinylpyrrolidone) (PVP) microneedle patches followed by coating with a phase change material 1-tetradecanol (TD). After placing in an aqueous solution or biofilm containing wounds ex vivo and in vivo, upon exposure to NIR light, the incorporated IR780 induces light-to-heat conversion, causing the melting of TD. This leads to the dissolution of PVP microneedles, enabling the release of loaded W379 peptide from the microneedles into surrounding regions (e.g., solution, biofilm, wound bed). Compared with traditional microneedle patches, NIR light responsive microneedle patches can program the release of antimicrobial peptide and show high antibacterial efficacy in vitro. Meanwhile, this work indicates that NIR light responsive TD-coated, W379-loaded PVP microneedle patches show excellent antibiofilm activities ex vivo and in vivo. Additionally, this microneedle system could be a promising platform for delivering other antimicrobial agents.

Role of Intraoperative Coeliac Plexus Neurolysis on Postoperative Pain Management for Chronic Pancreatitis.

Control of pain in patients with chronic pancreatitis is difficult because 30.0% to 50.0% of patients still experience persistence or recurrence of pain even after surgery. So a combined approach of surgery and coeliac plexus neurolysis was carried out in this study to see the relief of pain and reduce the requirement of analgesics in these patients. This prospective observational comparative study was carried out in the Department of Hepatobiliary, Pancreatic and Liver Transplant Surgery in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from November 2017 to October 2018. Forty one (41) study participants with the diagnosis of chronic pancreatitis were included consecutively in this study. The participants were divided into two groups. Group I (n=18) underwent pancreatic surgery with coeliac plexus neurolysis by infiltration of 20ml of 100% alcohol in the loose areolar tissue 10ml each into right and left para-aortic space at the level of coeliac trunk and Group II (n=23) underwent pancreatic surgery only. Participants' preoperative data were collected from patient record file. Number, frequency and intensity of pain and requirement of amount of analgesics for the last 3 months were recorded from patients' history. The intensity of pain was categorized by visual analog scale (VAS) preoperatively. The participants of both groups were followed up at 1, 2 and 3 months interval and asked for disappearance or reduction of pain, frequency of attack and requirement of analgesics. Again visual analog scale was used for categorization of pain. Pain free period was recorded after the end of follow up period. Pain reduction occurred after surgery in both groups. But when pain relief was compared on the basis of VAS (Visual Analogue Scale), it was significantly better in Group I after 1 month of surgery than Group II (p=0.05). But 2 and 3 months after surgery this difference became insignificant (p=0.246 and 0.264). No statistical difference was found in terms of analgesic usage, severe acute attack or hospital admission (p=0.511, 0.439 and 0.495) at the end of 3 months follow up. Participants in Group I had significantly longer pain free period than Group II (p=0.025). Regarding complications, postural hypotension developed in 5.6% (1) patients. Diarrhea developed in 11.1% (2) patients in Group I and wound infection developed in 2 patients in each groups respectively. No patients developed any major complications like anastomotic leakage, deep or organ or space infection. Intraoperative coeliac plexus neurolysis reduces pain immediately after surgery and provides longer pain free period in patients with chronic pancreatitis after surgery.

Nanofiber Aerogels with Precision Macrochannels and LL-37-Mimic Peptides Synergistically Promote Diabetic Wound Healing.

Fast healing of diabetic wounds remains a major clinical challenge. Herein, this work reports a strategy to combine nanofiber aerogels containing precision macrochannels and the LL-37-mimic peptide W379 for rapid diabetic wound healing. Nanofiber aerogels consisting of poly(glycolide-co-lactide) (PGLA 90:10)/gelatin and poly-p-dioxanone (PDO)/gelatin short electrospun fiber segments were prepared by partially anisotropic freeze-drying, crosslinking, and sacrificial templating with three-dimensional (3D)-printed meshes, exhibiting nanofibrous architecture and precision micro-/macrochannels. Like human cathelicidin LL-37, W379 peptide at a concentration of 3 µg/mL enhanced the migration and proliferation of keratinocytes and dermal fibroblasts in a cell scratch assay and a proliferation assay. In vivo studies show that nanofiber aerogels with precision macrochannels can greatly promote cell penetration compared to aerogels without macrochannels. Relative to control and aerogels with and without macrochannels, adding W379 peptides to aerogels with precision macrochannels shows the best efficacy in healing diabetic wounds in mice in terms of cell infiltration, neovascularization, and re-epithelialization. The fast re-epithelization could be due to upregulation of phospho-extracellular signal-regulated kinase (p38 MAPK) after treatment with W379. Together, the approach developed in this work could be promising for the treatment of diabetic wounds and other chronic wounds.

Recent Advances in Functional Wound Dressings.

Significance: Nowadays, the wound dressing is no longer limited to its primary wound protection ability. Hydrogel, sponge-like material, three dimensional-printed mesh, and nanofiber-based dressings with incorporation of functional components, such as nanomaterials, growth factors, enzymes, antimicrobial agents, and electronics, are able to not only prevent/treat infection but also accelerate the wound healing and monitor the wound-healing status. Recent Advances: The advances in nanotechnologies and materials science have paved the way to incorporate various functional components into the dressings, which can facilitate wound healing and monitor different biological parameters in the wound area. In this review, we mainly focus on the discussion of recently developed functional wound dressings. Critical Issues: Understanding the structure and composition of wound dressings is important to correlate their functions with the outcome of wound management. Future Directions: "All-in-one" dressings that integrate multiple functions (e.g., monitoring, antimicrobial, pain relief, immune modulation, and regeneration) could be effective for wound repair and regeneration.

Extracellular Matrix Secretion Mechanically Reinforces Interlocking Interfaces.

Drawing inspiration for biomaterials from biological systems has led to many biomedical innovations. One notable bioinspired device, Velcro, consists of two substrates with interlocking ability. Generating reversibly interlocking biomaterials is an area of investigation, as such devices can allow for modular tissue engineering, reversibly interlocking biomaterial interfaces, or friction-based coupling devices. Here, a biaxially interlocking interface generated using electrostatic flocking is reported. Two electrostatically flocked substrates are mechanically and reversibly interlocked with the ability to resist shearing and compression forces. An initial high-throughput screen of polyamide flock fibers with varying diameters and fiber lengths is conducted to elucidate the roles of different fiber parameters on scaffold mechanical properties. After determining the most desirable parameters via weight scoring, polylactic acid (PLA) fibers are used to emulate the ideal scaffold for in vitro use. PLA flocked scaffolds are populated with osteoblasts and interlocked. Interlocked flocked scaffolds improved cell survivorship under mechanical compression and sustained cell viability and proliferation. Additionally, the compression and shearing resistance of cell-seeded interlocking interfaces increased with increasing extracellular matrix deposition. The introduction of extracellular matrix-reinforced interlocking interfaces may serve as binders for modular tissue engineering, act as scaffolds for engineering tissue interfaces, or enable friction-based couplers for biomedical applications.

Next-Generation 3D Scaffolds for Nano-Based Chemotherapeutics Delivery and Cancer Treatment.

Cancer is the leading cause of death after cardiovascular disease. Despite significant advances in cancer research over the past few decades, it is almost impossible to cure end-stage cancer patients and bring them to remission. Adverse effects of chemotherapy are mainly caused by the accumulation of chemotherapeutic agents in normal tissues, and drug resistance hinders the potential therapeutic effects and curing of this disease. New drug formulations need to be developed to overcome these problems and increase the therapeutic index of chemotherapeutics. As a chemotherapeutic delivery platform, three-dimensional (3D) scaffolds are an up-and-coming option because they can respond to biological factors, modify their properties accordingly, and promote site-specific chemotherapeutic deliveries in a sustainable and controlled release manner. This review paper focuses on the features and applications of the variety of 3D scaffold-based nano-delivery systems that could be used to improve local cancer therapy by selectively delivering chemotherapeutics to the target sites in future.

Nanofiber capsules for minimally invasive sampling of biological specimens from gastrointestinal tract.

Accurate and rapid point-of-care tissue and microbiome sampling is critical for early detection of cancers and infectious diseases and often result in effective early intervention and prevention of disease spread. In particular, the low prevalence of Barrett's and gastric premalignancy in the Western world makes population-based endoscopic screening unfeasible and cost-ineffective. Herein, we report a method that may be useful for prescreening the general population in a minimally invasive way using a swallowable, re-expandable, ultra-absorbable, and retrievable nanofiber cuboid and sphere produced by electrospinning, gas-foaming, coating, and crosslinking. The water absorption capacity of the cuboid- and sphere-shaped nanofiber objects is shown ∼6000% and ∼2000% of their dry mass. In contrast, unexpanded semicircular and square nanofiber membranes showed <500% of their dry mass. Moreover, the swallowable sphere and cuboid were able to collect and release more bacteria, viruses, and cells/tissues from solutions as compared with unexpanded scaffolds. In addition to that, an expanded sphere shows higher cell collection capacity from the esophagus inner wall as compared with the unexpanded nanofiber membrane. Taken together, the nanofiber capsules developed in this study could provide a minimally invasive method of collecting biological samples from the duodenal, gastric, esophagus, and oropharyngeal sites, potentially leading to timely and accurate diagnosis of many diseases. STATEMENT OF SIGNIFICANCE: Recently, minimally invasive technologies have gained much attention in tissue engineering and disease diagnosis. In this study, we engineered a swallowable and retrievable electrospun nanofiber capsule serving as collection device to collect specimens from internal organs in a minimally invasive manner. The sample collection device could be an alternative endoscopy to collect the samples from internal organs like jejunum, stomach, esophagus, and oropharynx without any sedation. The newly engineered nanofiber capsule could be used to collect, bacteria, virus, fluids, and cells from the abovementioned internal organs. In addition, the biocompatible and biodegradable nanofiber capsule on a string could exhibit a great sample collection capacity for the primary screening of Barret Esophagus, acid reflux, SARS-COVID-19, Helicobacter pylori, and gastric cancer.

Pore Size-Dependent Stereoscopic Hydrogels Enhance the Therapeutic Efficiency of Botulinum Toxin for the Treatment of Nerve-Related Diseases.

Botulinum toxin (BoNT) is a major neurotherapeutic protein that has been used at low doses for diverse pharmacological applications. However, the pleiotropic effect of BoNT depends on multiple periodic injections owing to its rapid elimination profile, short-term therapeutic effect, and high mortality rate when administered at high doses. In addition to low patient compliance, these drawbacks represent the significant challenges that limit the further clinical use of BoNT. This study developed a new hydrogel-based single dosage form of BoNT by employing a one-step cross-linking chemistry. Its controlled porous structures and composition facilitated uniform drug distribution inside the hydrogel and controllable release of BoNT mediated by slow diffusion. A single dose remained stable for at least 2.5 months and showed sustained effect for at least 20 weeks, meeting the requirements for a single-dose form of BoNT. Additionally, this dosage form was evaluated as safe from all aspects of toxicology. This delivery system resulted in a 100% survival rate after administering a BoNT dose of 30 units, while a dose of more than 5 units of naked BoNT caused a 100% mortality rate within a few days. Overall, this strategy could provide patients with the first single-dose treatment option of BoNT and improve their quality of life.

Engineered Nanoparticles inside a Microparticle Oral System for Enhanced Mucosal and Systemic Immunity.

Antigen delivery through an oral route requires overcoming multiple challenges, including gastrointestinal enzymes, mucus, and epithelial tight junctions. Although each barrier has a crucial role in determining the final efficiency of the oral vaccination, transcytosis of antigens through follicle-associated epithelium (FAE) represents a major challenge. Most of the research is focused on delivering an antigen to the M-cell for FAE transcytosis because M-cells can easily transport the antigen from the luminal site. However, the fact is that the M-cell population is less than 1% of the total gastrointestinal cells, and most of the oral vaccines have failed to show any effect in clinical trials. To challenge the current dogma of M-cell targeting, in this study, we designed a novel tandem peptide with a FAE-targeting peptide at the front position and a cell-penetrating peptide at the back position. The tandem peptide was attached to a smart delivery system, which overcomes the enzymatic barrier and the mucosal barrier. The result showed that the engineered system could target the FAE (enterocytes and M-cells) and successfully penetrate the enterocytes to reach the dendritic cells located at the subepithelium dome. There was successful maturation and activation of dendritic cells in vitro confirmed by a significant increase in maturation markers such as CD40, CD86, presentation marker MHC I, and proinflammatory cytokines (TNF-α, IL-6, and IL-10). The in vivo results showed a high production of CD4+ T-lymphocytes (helper T-cell) and a significantly higher production of CD8+ T-lymphocytes (killer T-cell). Finally, the production of mucosal immunity (IgA) in the trachea, intestine, and fecal extracts and systemic immunity (IgG, IgG1, and IgG2a) was successfully confirmed. To the best of our knowledge, this is the first study that designed a novel tandem peptide to target the FAE, which includes M-cells and enterocytes rather than M-cell targeting and showed that a significant induction of both the mucosal and systemic immune response was achieved compared to M-cell targeting.

Graphene: A Promising Theranostic Agent.

Graphene has drawn tremendous interest in the field of nanoscience as a superior theranostic agent owing to its high photostability, aqueous solubility, and low toxicity. This monoatomic thick building block of a carbon allotrope exhibits zero to two-dimensional characteristics with a unique size range within the nanoscale. Their high biocompatibility, quantum yield, and photoluminescent properties make them more demandable in biomedical research. Its application in biomedical sciences has been limited due to its small-scale production. Large-scale production with an easy synthesis process is urgently required to overcome the problem associated with its translational application. Despite all possible drawbacks, the graphene-based drug/gene delivery system is gaining popularity day by day. To date, various studies suggested its application as a theranostic agent for target-specific delivery of chemotherapeutics or antibiotics against various diseases like cancer, Alzheimer's diseases, multidrug resistance diseases, and more. Also, studying the toxicological profile of graphene derivatives is very important before starting its practical use in clinical applications. This chapter has tried to abbreviate several methods and their possible incoming perspective as claimed by researchers for mass production and amplifying graphene-based treatment approaches.

ANTi-Vax: a novel Twitter dataset for COVID-19 vaccine misinformation detection.

OBJECTIVES: COVID-19 (SARS-CoV-2) pandemic has infected hundreds of millions and inflicted millions of deaths around the globe. Fortunately, the introduction of COVID-19 vaccines provided a glimmer of hope and a pathway to recovery. However, owing to misinformation being spread on social media and other platforms, there has been a rise in vaccine hesitancy which can lead to a negative impact on vaccine uptake in the population. The goal of this research is to introduce a novel machine learning-based COVID-19 vaccine misinformation detection framework. STUDY DESIGN: We collected and annotated COVID-19 vaccine tweets and trained machine learning algorithms to classify vaccine misinformation. METHODS: More than 15,000 tweets were annotated as misinformation or general vaccine tweets using reliable sources and validated by medical experts. The classification models explored were XGBoost, LSTM, and BERT transformer model. RESULTS: The best classification performance was obtained using BERT, resulting in 0.98 F1-score on the test set. The precision and recall scores were 0.97 and 0.98, respectively. CONCLUSION: Machine learning-based models are effective in detecting misinformation regarding COVID-19 vaccines on social media platforms.

Plasmid DNA Nanoparticles for Nonviral Oral Gene Therapy.

Herein, a bile acid-inspired triple padlock oral gene delivery platform is developed, facilitating the protection of the therapeutic gene from gastrointestinal degradation, selective intestinal accumulation through a bile acid-specific transporter, and transportation of pDNA NPs through the enterohepatic recycling system. This nonviral oral gene delivery nanoparticle exhibits excellent gene expression kinetics in in vitro, in vivo, and ex vivo studies. A single oral dose leads to maintaining normoglycemia for up to 7 days in three different diabetes mouse models and 14 days in diabetic monkeys. Also, the optimized dosage form can reduce nonfast blood glucose levels and hemoglobin A1C within a normal range from the last stage diabetes conditions with a reduction of weight gain from changes of food uptake behavior after treatment once weekly for 20 weeks. Taken together, the current findings could improve the current painful treatment experience of diabetics and thus improve their quality of life.