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Electroporation temporarily enhances cell membrane permeability and promotes the absorption of external molecules. We have developed a device termed the rolling microneedle electrode array (RoMEA) that combines a densely arranged microneedle array of electrodes with rolling structures. Use RoMEA to create uniform skin micropores for efficient, low-damage transfection of nucleic acids over extended areas of the body. We describe in detail the design, fabrication, and assembly of the device and the application of in vivo electroporation of nucleic acids. For complete details on the use and execution of this protocol, please refer to Tongren Yang et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Myasthenia gravis (MG) is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. The evidence suggests that the regulation of long noncoding RNAs (lncRNAs) that is mediated by transcription factors (TFs) plays a key role in the pathophysiology of MG. Nevertheless, the detailed molecular mechanisms of lncRNAs in MG remain largely undetermined., Methods: Using microarray analysis, we analyzed the lncRNA levels in MG. By bioinformatics analysis, LINC01566 was found to potentially play an important role in MG. First, qRT‒PCR was performed to verify the LINC1566 expressions in MG patients. Then, fluorescence in situ hybridization was conducted to determine the localization of LINC01566 in CD4 + T cells. Finally, the impact of LINC01566 knockdown or overexpression on CD4 + T-cell function was also analyzed using flow cytometry and CCK-8 assay. A dual-luciferase reporter assay was used to validate the binding of the TF FOSL1 to the LINC01566 promoter., Results: Based on the lncRNA microarray and differential expression analyses, we identified 563 differentially expressed (DE) lncRNAs, 450 DE mRNAs and 19 DE TFs in MG. We then constructed a lncRNA-TF-mRNA network. Through network analysis, we found that LINC01566 may play a crucial role in MG by regulating T-cell-related pathways. Further experiments indicated that LINC01566 is expressed at low levels in MG patients. Functionally, LINC01566 is primarily distributed in the nucleus and can facilitate CD4 + T-cell apoptosis and inhibit cell proliferation. Mechanistically, we hypothesized that LINC01566 may negatively regulate the expressions of DUSP3, CCR2, FADD, SIRPB1, LGALS3 and SIRPB1, which are involved in the T-cell activation pathway, to further influence the cellular proliferation and apoptosis in MG. Moreover, we found that the effect of LINC01566 on CD4 + T cells in MG was mediated by the TF FOSL1, and in vitro experiments indicated that FOSL1 can bind to the promoter region of LINC01566., Conclusions: In summary, our research revealed the protective roles of LINC01566 in clinical samples and cellular experiments, illustrating the potential roles and mechanism by which FOSL1/LINC01566 negatively regulates CD4 + T-cell activation in MG., (© 2024. The Author(s).)

Excessive peroxynitrite (ONOO - ) is closely related to the occurrence and progression of inflammation. Therefore, the development of an efficacious ONOO - activatable probe holds great potential for the early diagnosis of pathological inflammation, and the direct evaluation of the therapeutic efficacy of active protectants. In this work, a new ONOO - -activated fluorescent probe (SZP) which greatly improved the specificity and sensitivity (LOD = 8.03 nM) with large Stokes shift (150 nm) through introducing two reaction triggers (diphenyl phosphinate moiety, CC unsaturated bond) was rationally designed for rapid detecting ONOO - (within 2 min). The excellent properties of probe SZP enable it to realize the fluorescence-guided diagnosis of inflammation. More importantly, probe SZP has also been utilized to assess the anti-inflammatory efficacy of traditional Chinese medicines (TCMs) active ingredients for the remediation of inflammation by monitoring ONOO - fluctuation for the first time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Microneedle drug delivery has recently emerged as a clinical method, and dissolving microneedles (DMNs) offer exclusive simplicity and efficiency, compared to the other kinds of microneedles. The tips of most currently available DMNs are cone/house-shaped to result in a lower penetration force. Penetration of the needle tips into the skin relies mainly on the back tape or external pressure, and their adhesion to the skin is relatively low. In addition, only the drug in the part of tips that are pierced into the dermis can be dissolved, resulting in drug waste. Inspired from the barbed structure of the honeybee stinger, we reported substrate-free DMNs with a barbed structure by a dual-molding process, which is suitable for mass production. Those DMNs showed 3-fold greater adhesion force between the needle tips and the skin, better dissolution and deeper penetration than house-shaped DMNs in vivo under the same conditions. For the in situ treatment of psoriasis in mice, the barbed DMNs required only the half dose of house-shaped DMNs to achieve similar efficacy., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Salvia miltiorrhiza Bunge (Labiatae) (DS) is a key part of the traditional Chinese medicine, whose roots are used to remove blood stasis, relieve pain, eliminate carbuncle and calm the nerves. Our research team found that the DS extract could significantly reverse LPS-induced lung injury, and five new diterpenoid quinones in DS extract with excellent lung protective activity for the first time. However, the material basis and mechanism of DS on pulmonary fibrosis (PF) needs to be explored in depth., Objective: Bleomycin (BLM) was employed to establish the PF model, and Transcriptome and Surface plasmon resonance (SPR) ligand fishing technology were used to explore the material basis and mechanism of DS on PF, and provided theoretical research for clinical treatment of PF., Methods: DS extract (24.58 or 49.16 mg/kg, i.g.) was administered daily from Day 8 to Day 28, followed by intratracheal BLM drip (5 mg/kg) to induce PF. Data about the influences of DS on PF were collected by transcriptome sequencing technology. Pulmonary ultrasound, airway responsiveness, lung damage, collagen deposition, and the levels of TNF-α, IL-1β, apoptosis, oxidative stress (OS), immune cells, TGF-β1, α-SMA, E-Cadherin and Collage Ⅰ were examined. The affinity component (Przewalskin) in DS extract targeted by TGF-β1 was fished by SPR ligand fishing technology. Furthermore, an in vivo PF mouse model and an in vitro TGF-β1 induced BEAS-2B cell model were established, to explore the mechanism of Przewalskin on PF from the apoptosis, OS and epithelial mesenchymal transformation pathway., Results: DS extract improved pulmonary ultrasound, reduced lung damage and collagen deposition, downregulated TNF-α, IL-1β, apoptosis, OS, TGF-β1, α-SMA, E-Cadherin and Collage Ⅰ, transformed immune cells following Bleomycin challenge. Furthermore, affinity component (Przewalskin) also improved pulmonary ultrasound and airway responsiveness, reduced lung damage and collagen deposition, downregulated TNF-α, IL-1β, apoptosis, OS in vivo and in vitro., Conclusion: Analysis using a mouse model revealed that DS extract and Przewalskin can relieve clinical symptoms of PF, reduce lung injury and improve lung function. Meanwhile, DS extract and Przewalskin can improve BLM-induced PF by inhibition of, OS, apoptosis and collagen deposition might via the TGF-β1 pathway. This study provides references to identification of novel therapeutic targets, thereby facilitating drug development for PF., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Nucleic acids, including DNA and RNA, have been considered as powerful and functional biomaterials owing to their programmable structure, good biocompatibility, and ease of synthesis. However, traditional nucleic acid-based probes have always suffered from inherent limitations, including restricted cell internalization efficiency and structural instability. In recent years, DNA nanotechnology has shown great promise for the applications of bioimaging and drug delivery. The attractive superiorities of DNA nanostructures, such as precise geometries, spatial addressability, and improved biostability, have enabled them to be a novel category of nucleic acid delivery systems for biomedical applications. In this review, we introduce the development of DNA nanotechnology, and highlight recent advances of DNA nanostructure-based delivery systems for cellular imaging and therapeutic applications. Finally, we propose the challenges as well as opportunities for the future development of DNA nanotechnology in biomedical research.

Six new compounds, (7 R ,8 S ,8' R )-balanophorone ( 1 ), (7' S ,8' R ,8 R )-yunnanensin A ( 2 ), (3 S )-thunberginol C ( 3 ), (8 R ,8' R )-maninsigin B ( 4 ), (7 S ,8 R )-4,7,8-dihydroxy-9,9-dimethyl-chroman ( 5 ), and 4-hydroxy-1-(4-hydroxy-3-methoxyphenyl)butan-1-one ( 6 ), along with eight known compounds ( 7 - 14 ), were isolated from the herbaceous stems of Ephedra intermedia Schrenket C. A. Meyer. Their structures were elucidated based on their spectroscopic (MS, NMR, IR, and UV) data, and their absolute configurations were determined by comparing their calculated and experimental electronic circular dichroic (ECD) spectra. Moreover, compounds 1 and 3 - 6 were evaluated for their ability to protect human pulmonary epithelial cells (BEAS-2B) from injury induced by lipopolysaccharide (LPS) in vitro. The results showed that compound 6 exhibited a significant protective effect against LPS-induced injury in BEAS-2B, and compound 5 exhibited a slightly protective effect at the concentration of 10 μM.

Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device's soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention., (© 2024. The Author(s).)

Microneedles, especially hollow microneedles (HMNs), play an important role in drug delivery, but most of the current HMNs are manufactured based on silicon microfabrication (lithography, etching, etc.), which are slightly conservative due to the lack of low-cost, batch-scale and customized preparation approach, especially for the HMNs with flexible substrate. For the first time, we propose the use of a high-precision 3D printed master mold followed by a dual-molding process for the preparation of HMNs with different shapes, heights, and inner and outer diameters to satisfy different drug delivery needs. The 3D printed master mold and negative mold can be reused, thereby significantly reducing the cost. HMNs are based on biocompatible materials, such as heat-curing polymers or light-curing resins. The thickness and rigidity/flexibility characteristics of the substrate can be customized for different applications. The drug delivery efficiency of the fabricated HMNs was verified by the in situ treatment of psoriasis on the backs of mice, which required only a 0.1-fold oral dose to achieve similar efficacy, and the associated side effects and drug toxicity were reduced. Thus, this dual-molding process can reinvigorate HMNs development., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Monitoring sleep conditions is of importance for sleep quality evaluation and sleep disease diagnosis. Accurate respiration detection provides key information about sleep conditions. Here, we propose a perforated temperature sensor that can be worn below the nasal cavity to monitor breath. The sensing system consists of two perforated temperature sensors, signal conditioning circuits, a transmission module, and a supporting analysis algorithm. The perforated structure effectively enhances the sensitivity of the system and shortens the response time. The sensor's response time is 0.07 s in air and sensitivity is 1.4‱°C -1 . The device can achieve a monitoring respiratory temperature range between normal room temperature and 40 °C. The simple and standard micromachining process ensures low cost and high reproducibility. We achieved the monitoring of different breathing patterns, such as normal breathing, panting, and apnea, which can be applied to sleep breath monitoring and exercise information recording.

Background: Severe inflammation of the lungs results from acute lung injury (ALI), a common life-threatening lung disease with a high mortality rate. The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) γ plays essential roles in diverse biological processes including inflammation, metabolism, development, and immune response. Salvianolactone acid A (SA) is a terpenoid derived from the herb Salvia miltiorrhiza. However, there is a scarcity of experimental evidence indicating whether the effect of SA on ALI occurs via PPAR-γ., Methods: SA (20 or 40 mg/kg, i.g., 1 time/day) was administered to mice for 3 d, followed by the induction of ALI by intranasal lipopolysaccharide (LPS, 10 mg/kg). The lung function and levels of inflammation, reactive oxygen species (ROS), immune cells, apoptosis, and PPAR-γ were examined. The antagonistic activity of GW9662 (GW, 1 µM, specific PPAR-γ blocker) and PPAR-γ transfection silencing against SA (10 μM) in BEAS-2B cells induced by LPS (10 μg/ml, 24 h) was also investigated to assess whether the observed effects caused by SA were mediated by PPAR-γ., Results: The results showed that lung histopathological injury, the B-line, the fluorescence intensity of live small animal, and the biomarkers in BALF or lung in the treatment of SA could regulate significantly. In addition, SA obviously decreased the levels of ROS and apoptosis in the primary lung cells, and MDA, increased the levels of GSH-Px and SOD. SA reduced levels of macrophages and neutrophils. Furthermore, SA reduced the protein levels of Keap-1, Cleaved-caspase-3, Cleaved-caspase-9, p-p65/p65, NLRP3, IL-1β, and upregulated the levels of p-Nrf2/Nrf2, HO-1, Bcl-2/Bax, PPAR-γ, p-AMPK/AMPK in lung tissue. In addition, silencing and inhibition of PPAR-γ effectively decreased the protective effects of SA in BEAS-2B cells induced by LPS, which might indicate that the active molecules of SA regulate ALI via mediation by PPAR-γ, which exhibited that the effect of SA related to PPAR-γ., Conclusions: The anti-ALI effects of SA were partially mediated through PPAR-γ signaling. These data provide the molecular justification for the usage of SA in treating ALI and can assist in increasing the comprehensive utilization rate of Salvia miltiorrhiza., (Copyright © 2022. Published by Elsevier GmbH.)

Acute lung injury (ALI) is a common critical disease with a high mortality rate. Natural products have marked efficacy in the prevention and treatment of ALI, in addition, estrogen and its receptors are involved in the pathogenesis and development of lung injury. Our previous research shows that sesquiterpenes isolated from the stems and leaves of Dioscorea opposita Thunb. have anti-inflammatory and estrogenic-like activity. In the present study, sesquiterpene (A1) is a natural extract from the stems and leaves of Dioscorea opposita Thunb. with a view to determining whether A1 can improve lung function in a mouse model of LPS-induced ALI and exploring the involvement of the estrogen receptor β (ER β ) pathway. A1 (20 or 40 mg/kg, i. g., 2 times/day) was administered for 3 d, followed by the induction of ALI via an intratracheal LPS drip (5 mg/kg/2 h). The lung function and levels of inflammation, immune cells, apoptosis, and ER β expression were examined. The antagonistic activity of specific ER β blocker (THC, 1 μM) against A1 (20 μM) in co-cultured BEAS-2B cells and splenic lymphocytes induced with LPS (1 μg/mL, 24 h) was also investigated to assess whether the observed effects of A1 were mediated by ER β . A1 improved lung function, regulated the immune system, and decreased inflammation and apoptosis. Moreover, A1 increased the expression of ER β in LPS-induced mice, and antagonism of ER β decreased the protective effects of A1 in a co-culture system. A1 had anti-ALI effects that might partially mediated through ER β signaling. Our data provide molecular justification for the use of A1 in the treatment of ALI., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Highlights: Polyimide-based flexible microneedle array (PI-MNA) electrodes realize high electrical/mechanical performance and are compatible with wearable wireless recording systems. The normalized electrode-skin interface impedance (EII) of the PI-MNA electrodes reaches 0.98 kΩ cm 2 at 1 kHz and 1.50 kΩ cm 2 at 10 Hz, approximately 1/250 of clinical standard electrodes. This is the first report on the clinical study of microneedle electrodes. The PI-MNA electrodes are applied to clinical long-term continuous monitoring for polysomnography. Microneedle array (MNA) electrodes are an effective solution to achieve high-quality surface biopotential recording without the coordination of conductive gel and are thus very suitable for long-term wearable applications. Existing schemes are limited by flexibility, biosafety, and manufacturing costs, which create large barriers for wider applications. Here, we present a novel flexible MNA electrode that can simultaneously achieve flexibility of the substrate to fit a curved body surface, robustness of microneedles to penetrate the skin without fracture, and a simplified process to allow mass production. The compatibility with wearable wireless systems and the short preparation time of the electrodes significantly improves the comfort and convenience of electrophysiological recording. The normalized electrode-skin contact impedance reaches 0.98 kΩ cm 2 at 1 kHz and 1.50 kΩ cm 2 at 10 Hz, a record low value compared to previous reports and approximately 1/250 of the standard electrodes. The morphology, biosafety, and electrical/mechanical properties are fully characterized, and wearable recordings with a high signal-to-noise ratio and low motion artifacts are realized. The first reported clinical study of microneedle electrodes for surface electrophysiological monitoring was conducted in tens of healthy and sleep-disordered subjects with 44 nights of recording (over 8 h per night), providing substantial evidence that the electrodes can be leveraged to substitute for clinical standard electrodes., (© 2022. The Author(s).)

A new flavonoid, saffloflavanside ( 1 ), a new sesquiterpene, safflomegastigside ( 2 ), and a new amide, saffloamide ( 3 ), together with twenty-two known compounds ( 4 - 25 ), were isolated from the flowers of Carthamus tinctorius L. Their structures were determined based on interpretation of their spectroscopic data and comparison with those reported in the literature. The protective effects against lipopolysaccharide (LPS)-stimulated damage on human normal lung epithelial (BEAS-2B) cells of the compounds were evaluated using MTT assay and cellular immunofluorescence assay. The results showed that compounds 2 - 3 , 8 - 11 , and 15 - 19 exhibited protective effects against LPS-induced damage to BEAS-2B cells. Moreover, compounds 2 - 3 , 8 - 11 , and 15 - 19 can significantly downregulate the level of nuclear translocation of NF-κB p-p65. In summary, this study revealed chemical constituents with lung protective activity from C. tinctorius , which may be developed as a drug for the treatment of lung injury.

If not cured promptly, tissue ischemia and hypoxia can cause serious consequences or even threaten the life of the patient. Hemoglobin-based oxygen carrier-201 (HBOC-201), bovine hemoglobin polymerized by glutaraldehyde and stored in a modified Ringer's lactic acid solution, has been investigated as a blood substitute for clinical use. HBOC-201 was approved in South Africa in 2001 to treat patients with low hemoglobin (Hb) levels when red blood cells (RBCs) are contraindicated, rejected, or unavailable. By promoting oxygen diffusion and convective oxygen delivery, HBOC-201 may act as a direct oxygen donor and increase oxygen transfer between RBCs and between RBCs and tissues. Therefore, HBOC-201 is gradually finding applications in treating various ischemic and hypoxic diseases including traumatic hemorrhagic shock, hemolysis, myocardial infarction, cardiopulmonary bypass, perioperative period, organ transplantation, etc. However, side effects such as vasoconstriction and elevated methemoglobin caused by HBOC-201 are major concerns in clinical applications because Hbs are not encapsulated by cell membranes. This study summarizes preclinical and clinical studies of HBOC-201 applied in various clinical scenarios, outlines the relevant mechanisms, highlights potential side effects and solutions, and discusses the application prospects. Randomized trials with large samples need to be further studied to better validate the efficacy, safety, and tolerability of HBOC-201 to the extent where patient-specific treatment strategies would be developed for various clinical scenarios to improve clinical outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cao, Zhao, He, Yue, Pan, Hu, Ren, Qin, Yi, Yin, Ma, Zhang and Huang.)

Lung cancer is the most leading cause of cancer mortality throughout the world, of which about 85% cases comprise the non-small cell lung cancer (NSCLC). Estrogen and estrogen receptors are known to be involved in the pathogenesis and development of lung cancer. Dioscorea oppositifolia L. is a traditional Chinese medicine and a nutritious food, and can be an excellent candidate as an anti-cancer agent owing to its estrogen-like effects. However, the stems and leaves of D. oppositifolia L. are piled up in the field as a waste, causing environmental pollution and waste of resources. In the present study, a new diphenylethane (D1) was isolated from the stems and leaves of D. oppositifolia L. It was observed that D1 reduced the cell viability, migration, energy metabolism, and induced apoptosis in the A549 cells. Mechanistic studies showed that D1 reduced the STAT3 nuclear localization and downregulated the expression of the STAT3 target genes like Mcl-1, Bcl-xL and MMP-2 that are involved in the cell survival and mobility. Moreover, our results indicated that D1 exhibited estrogenic activities mediated by ER β , and antagonising ER β decreased the cytotoxic effect of D1 in A549 cells. In addition, inhibition of the nuclear translocation of STAT3 did not interfere with the binding of D1 and ER β . However, after antagonizing ER β , the nuclear translocation of STAT3 increased, thereby demonstrating that STAT3 was the downstream signaling molecule of ER β . In conclusion, the D1 mediated anti-NSCLC in vitro effects or at least in part can be attributed to the ER β -STAT3 signaling. Our findings suggest the role of D1 in treating NSCLC on a molecular level, and can help to improve the comprehensive utilization rate of D. oppositifolia L., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zeng, Ren, Zhang, Wang, Liu, Jia, Guo, Zhang, Zheng and Feng.)

Thrombolysis is the main therapeutic method of acute pulmonary embolism (APE). In order to investigate the efficacy of reteplase on APE and the changes of cytokines in the progression of APE, 72 patients with APE were randomized into reteplase group and urokinase group which received reteplase thrombolysis and urokinase thrombolysis, respectively. The clinical symptoms, blood pressure, heart rate (HR), blood gas index and cytokines of patients were observed before and after therapy for assessing the thrombolysis effect of each group; blood level of high sensitive C-reactive protein (hs-CRP), TNF-α, IL-1β, IL-6 and IL-10 was detected at 0h, 2h, 6h, 12h and 24h after thrombolysis. After treatment, the clinical symptoms of both groups were alleviated obviously; PaO 2 , PaCO 2 , blood pressure and HR in both groups were significantly improved than those before treatment (p<0.001), and reteplase group showed a more obvious improvement than urokinase group (p<0.001). Since 6h after therapy, the content of hs-CRP, IL-1β and IL-6 in patients of reteplase group declined significantly (p<0.05 or 0.01). In conclusion, therapeutic effect of reteplase is better than urokinase, hs-CRP, IL-1β and IL-6 can be used to monitor the thrombolysis efficacy of APE patients.

A new supramolecular hydrogel self-assembled between α-cyclodextrin (α-CD) and a star-like block copolymer AE73 was prepared. The cooperation effect of complexation of poly-(ethylene oxide) (PEO) segments with α-CD and the hydrophobic interaction between poly-(propylene oxide) (PPO) blocks resulted in the formation of the supramolecular hydrogel with a strong macromolecular network. Then two kinds of carbon materials (graphene and graphene oxide) were successfully incorporated into the above α-CD/AE73 hydrogel to further enhance the mechanical properties. The native hydrogel, as well as hybrid hydrogels, have been thoroughly characterized by using various microscopic techniques, including transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA). Our main purpose is to ascertain whether the properties of the obtained gels depend on these architectures. Interestingly, the phase behavior, the morphology and the mechanical strength of the native hydrogel can be successfully modulated by incorporating graphene and graphene oxide. Taking into account that both PEO/PPO copolymers and α-CD seem to be biocompatible, these gels can be promising for biomedical applications., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

It is well known that exposure to UV induces DNA damage, which is the first step in mutagenesis and a major cause of skin cancer. Among a variety of photoproducts, cyclobutane-type pyrimidine photodimers (CPD) are the most abundant primary lesion. Despite its biological importance, the precise relationship between the structure and properties of DNA containing CPD has remained to be elucidated. Here, we report the free (unbound) crystal structure of duplex DNA containing a CPD lesion at a resolution of 2.0 A. Our crystal structure shows that the overall helical axis bends approximately 30 degrees toward the major groove and unwinds approximately 9 degrees, in remarkable agreement with some previous theoretical and experimental studies. There are also significant differences in local structure compared with standard B-DNA, including pinching of the minor groove at the 3' side of the CPD lesion, a severe change of the base pair parameter in the 5' side, and serious widening of both minor and major groves both 3' and 5' of the CPD. Overall, the structure of the damaged DNA differs from undamaged DNA to an extent that DNA repair proteins may recognize this conformation, and the various components of the replicational and transcriptional machinery may be interfered with due to the perturbed local and global structure.