The role of TNC in atherosclerosis and drug development opportunities.

Tenascin C (TNC), a rich glycoprotein of the extracellular matrix, exhibits a pro-atherosclerosis or anti-atherosclerosis effect depending on its location. TNC, especially its C domain/isoform (TNC-C), is strongly overexpressed in atherosclerotic plaque active areas but virtually undetectable in most normal adult tissues, suggesting that TNC is a promising delivery vector target for atherosclerosis-targeted drugs. Many delivery vectors were investigated by recognizing TNC-C, including G11, G11-iRGD, TN11, PL1, and PL3. F16 and FNLM were also investigated by recognizing TNC-A1 and TNC, respectively. Notably, iRGD was undergoing clinical trials. PL1 not only recognizes TNC-C but also the extra domain-B (EDB) of fibronectin (FN), which is also a promising delivery vector for atherosclerosis-targeted drugs, and several conjugate agents are undergoing clinical trials. The F16-conjugate agent F16IL2 is undergoing clinical trials. Therefore, G11-iRGD, PL1, and F16 have great development value. Furthermore, ATN-RNA and IMA950 were investigated in clinical trials as therapeutic drugs and vaccines by targeting TNC, respectively. Therefore, targeting TNC could greatly improve the success rate of atherosclerosis-targeted drugs and/or specific drug development. This review discussed the role of TNC in atherosclerosis, atherosclerosis-targeted drug delivery vectors, and agent development to provide knowledge for drug development targeting TNC.

Advanced function, design and application of skin substitutes for skin regeneration.

The development of skin substitutes aims to replace, mimic, or improve the functions of human skin, regenerate damaged skin tissue, and replace or enhance skin function. This includes artificial skin, scaffolds or devices designed for treatment, imitation, or improvement of skin function in wounds and injuries. Therefore, tremendous efforts have been made to develop functional skin substitutes. However, there is still few reports systematically discuss the relationship between the advanced function and design requirements. In this paper, we review the classification, functions, and design requirements of artificial skin or skin substitutes. Different manufacturing strategies for skin substitutes such as hydrogels, 3D/4D printing, electrospinning, microfluidics are summarized. This review also introduces currently available skin substitutes in clinical trials and on the market and the related regulatory requirements. Finally, the prospects and challenges of skin substitutes in the field of tissue engineering are discussed.

A novel nanobody-based HER2-targeting antibody exhibits potent synergistic antitumor efficacy in trastuzumab-resistant cancer cells.

Human epithelial growth factor receptor-2 (HER2) plays an oncogenic role in numerous tumors, including breast, gastric, and various other solid tumors. While anti-HER2 therapies are approved for the treatment of HER2-positive tumors, a necessity persists for creating novel HER2-targeted agents to resolve therapeutic resistance. Utilizing a synthetic nanobody library and affinity maturation, our study identified four anti-HER2 nanobodies that exhibited high affinity and specificity. These nanobodies recognized three distinct epitopes of HER2-ECD. Additionally, we constructed VHH-Fc and discovered that they facilitated superior internalization and showed moderate growth inhibition. Compared to the combination of trastuzumab and pertuzumab, the VHH-Fc combos or their combination with trastuzumab demonstrated greater or comparable antitumor activity in both ligand-independent and ligand-driven tumors. Most remarkably, A9B5-Fc, which targeted domain I of HER2-ECD, displayed significantly enhanced trastuzumab-synergistic antitumor efficacy compared to pertuzumab under trastuzumab-resistant conditions. Our findings offer anti-HER2 nanobodies with high affinity and non-overlapping epitope recognition. The novel nanobody-based HER2-targeted antibody, A9B5-Fc, binding to HER2-ECD I, mediates promising receptor internalization. It possesses the potential to serve as a potent synergistic partner with trastuzumab, contributing to overcoming acquired resistance.

Multi-material electrospinning: from methods to biomedical applications.

Electrospinning as a versatile, simple, and cost-effective method to engineer a variety of micro or nanofibrous materials, has contributed to significant developments in the biomedical field. However, the traditional electrospinning of single material only can produce homogeneous fibrous assemblies with limited functional properties, which oftentimes fails to meet the ever-increasing requirements of biomedical applications. Thus, multi-material electrospinning referring to engineering two or more kinds of materials, has been recently developed to enable the fabrication of diversified complex fibrous structures with advanced performance for greatly promoting biomedical development. This review firstly gives an overview of multi-material electrospinning modalities, with a highlight on their features and accessibility for constructing different complex fibrous structures. A perspective of how multi-material electrospinning opens up new opportunities for specific biomedical applications, i.e., tissue engineering and drug delivery, is also offered.

The clinical development of antibody-drug conjugates for non-small cell lung cancer therapy.

Despite the emergence of molecular targeted therapy and immune checkpoint inhibitors as standard first-line treatments for non-small cell lung cancer (NSCLC), their efficacy in some patients is limited by intrinsic and acquired resistance. Antibody-drug conjugates (ADCs), a revolutionary class of antitumor drugs, have displayed promising clinical outcomes in cancer treatment. In 2022, trastuzumab deruxtecan (Enhertu) was approved for treating HER2-mutated NSCLC, thereby underscoring the clinical value of ADCs in NSCLC treatment strategies. An increasing number of ADCs, focusing on NSCLC, are undergoing clinical trials, potentially positioning them as future treatment options. In this review, we encapsulate recent advancements in the clinical research of novel ADCs for treating NSCLC. Subsequently, we discuss the mechanisms of action, clinical efficacy, and associated limitations of these ADCs.

The role and transformative potential of IL-19 in atherosclerosis.

Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Traditionally, IL-19 was thought to be expressed in only immune cells, but studies revealed that IL-19 is also expressed in multiple atherosclerotic plaque cell types, but not normal arteries, in humans and mice. IL-19 reduces the development of atherosclerosis via multiple mechanisms, including balancing cholesterol metabolism; enhancing Th2 immune cell polarization; reducing the inflammatory response; and reducing the proliferation, migration and chemotaxis of vascular smooth muscle cells (VSMCs). Clinical and/or animal studies have primarily aimed to achieve regression and/or stabilization of atherosclerotic plaques, with regression in particular indicating a very good drug response. Most antiatherosclerotic drugs in current clinical use, including atorvastatin and alirocumab, target hyperlipidemia. Several other drugs have also been investigated in clinical trials as anti-inflammatory agents; the development of some of these agents has been terminated (canakinumab, darapladib, varespladib, losmapimod, atreleuton, setileuton, PF-04191834, veliflapon, and methotrexate), but others remain in development (ziltivekimab, tocilizumab, Somalix, IFM-2427, anakinra, mesenchymal stem cells (MSCs), colchicine, everolimus, allopurinol, and montelukast). Most of the tested drugs have shown a limited ability to reverse atherosclerosis in animal studies. Interestingly, recombinant IL-19 (rIL-19) was shown to reduce atherosclerosis development in a time- and dose-dependent manner. A low dose of rIL-19 (1 ng/g/day) reduced aortic arch and root plaque areas by 70.1% and 32.1%, respectively, in LDLR-/- mice. At 10 ng/g/day, rIL-19 completely eliminated atherosclerotic plaques. There were no sex differences in the effects of rIL-19 on atherosclerotic mice. Thus, low-dose rIL-19 is an effective antiatherosclerotic agent, in addition to its efficacy in intimal hyperplasia, spinal cord injury, stroke, and multiple sclerosis. We propose that IL-19 is a promising biomarker and target for the diagnosis and treatment of atherosclerosis. This review considers the role and mechanism of action of IL-19 in atherosclerosis and discusses whether IL-19 is a potential therapeutic target for this condition.

Comparison of totally laparoscopic and laparoscopic assisted gastrectomy after neoadjuvant chemotherapy in locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) and laparoscopic surgery have been increasingly used in the treatment of gastric cancer, however, the feasibility and safety of totally laparoscopic gastrectomy after NACT still remain unknown. MATERIALS AND METHODS: At the Gastrointestinal cancer center of Peking university cancer hospital and institute in Beijing, clinical and pathological data of patients who has received NACT, followed by radical laparoscopic gastrectomy was retrospectively reviewed between March 2011 and November 2019. Patients were divided into 2 groups according to whether intracorporeal anastomosis or extracorporeal anastomosis had been performed, short-term outcomes (post-operative recovery index and complications) and economic cost were compared between 2 groups. RESULT: All of 139 patients underwent laparoscopic gastrectomy. 87 [62.6%] patients had totally laparoscopic gastrectomy (TLG) and 52 [37.4%] patients had laparoscopic-assisted gastrectomy (LAG). Overall complication rate was 28.8% in all patients. TLG group was significantly associated with lower overall complication rate (21.8% VS 40.4%; p = 0.019) and major complication rate (3.4% VS 13.5%; p = 0.001) compared with LAG group. Overall cost was similar (p = 0.077). In subgroup analysis, totally laparoscopic total gastrectomy (TLTG) group showed lower overall postoperative complication rate (19.0% VS 56.5%; p = 0.011), as well as marginal significant differences in major complication (0% VS 21.7%; p = 0.05) than laparoscopic-assisted total gastrectomy (LATG) group. Earlier first liquid diet (4 [3.5-5] day VS 6 [4-6.5] day; p = 0.047), earlier first aerofluxus (3 [3-4] day VS 4 [3-4.5] day; p = 0.02) and a shorter hospital stay (9 [8-12] day VS 12 [10-15] day; p = 0.004) were observed in TLTG group. Overall and major complication rate were similar in totally laparoscopic distal gastrectomy (TLDG) and laparoscopic assisted distal gastrectomy (LADG) group (22.7% VS 27.6%; p = 0.611; 4.5% VS 6.9%; p = 0.639; respectively). Significant differences were found between TLDG and LADG groups regarding time to first liquid diet (4 [3-5] day VS 6 [3.75-6] day; p = 0.006), time to first aerofluxus (3 [3-3] day VS 4 [3-6] day; p< 0.001), time to first defecation (4 [4-5] day VS 5 [4-6] day; p = 0.045), time to remove all drainage (7 [6-8] day VS 8 [6-9] day; p = 0.021), white blood cell count on postoperative Day 1 (9.54 ± 2.49 109/L VS 10.91 ± 2.89 109/L; p = 0.021)and postoperative hospital stay (9 [8-10] day VS 10 [9,13] day; p = 0.009). CONCLUSION: For patients with Locally advanced gastric cancer who received NACT, totally laparoscopic gastrectomy, including TLTG and TLDG, doesn't increase complications and overall cost compared with LAG, and has advantages in gastrointestinal function recovery, incision length and postoperative hospital stay.

A single-step lithography system based on an enhanced robotic adhesive dispenser.

In the paper, we present a single-step lithography system whereby the robotically controlled micro-extrusion of resist adhesive onto a substrate surface to directly create resist adhesive patterns of interest. This system is modified from a robotic adhesive dispenser by shrinking the aperture of the nozzle to a few micrometers aiming to realize patterns at microscale. From experimental investigation, it is found that working factors including writing speed, working time, and applied pressure can be adopted to conveniently regulate the feature size (the width of the line features and the diameter of the dot features). To test its functionality, the system was used to pattern line features on silicon dioxide (SiO2) and generate an array of square-like silicon microstructure by combining with wet etching. It provides a simple and flexible alternative tool to facilitate the development of microfabrication.

Extrusion printing for fabrication of spherical and cylindrical microlens arrays.

In this paper, we present an extrusion printing technique for producing spherical and cylindrical plano-convex microlens arrays with controllable feature dimensions. This technique employs a robotic adhesive dispenser for robotically controlled microextrusion of ultraviolet (UV) curable polymer onto a glass substrate surface to directly deposit the microlens arrays. It provides a simple and flexible alternative to fabricate both spherical and cylindrical microlens arrays.