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Woo-Jin Jeon,1,* Hong-Ki Lee,2,3,* Young-Guk Na,1 Minwoo Jung,1 Su-Cheol Han,2 Jeong Ho Hwang,2 Eunhye Jung,4 Dasom Hwang,4 Jin Soo Shin,4 Cheong-Weon Cho1 1College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, 34134, Republic of Korea; 2Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology (KIT), Jeongeup, Jeollabuk-do, 53212, Republic of Korea; 3Human Health Risk Assessment Center, Jeonbuk Branch, Korea Institute of Toxicology (KIT), Jeongeup, Jeollabuk-do, 53212, Republic of Korea; 4Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea*These authors contributed equally to this workCorrespondence: Jin Soo Shin, Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea, Email jsshin@krict.re.kr Cheong-Weon Cho, College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea, Email chocw@cnu.ac.krIntroduction: The ongoing SARS-CoV-2 pandemic has affected public health, the economy, and society. This study reported a nanotechnology-based strategy to enhance the antiviral efficacy of the antiviral agent remdesivir (RDS).Results: We developed a nanosized spherical RDS-NLC in which the RDS was encapsulated in an amorphous form. The RDS-NLC significantly potentiated the antiviral efficacy of RDS against SARS-CoV-2 and its variants (alpha, beta, and delta). Our study revealed that NLC technology improved the antiviral effect of RDS against SARS-CoV-2 by enhancing the cellular uptake of RDS and reducing SARS-CoV-2 entry in cells. These improvements resulted in a 211% increase in the bioavailability of RDS.Conclusion: Thus, the application of NLC against SARS-CoV-2 may be a beneficial strategy to improve the antiviral effects of antiviral agents.Keywords: remdesivir, nanostructured lipid carrier, antiviral effect, SARS-CoV-2, virus entry

Exposure of agricultural workers in rice paddies to the insecticide chlorantraniliprole and its subsequent potential health risks were investigated during two scenarios (mixing/loading and hand-held spraying). The exposure factors, such as the outer dosimeter, inner dosimeter, gauze, and nitrile gloves, were calculated using whole-body dosimetry to measure dermal exposure. The inhalation exposure was determined using a fiberglass filter which is set with an Institute of Occupational Medicine (IOM) sampler. A recovery test was performed to evaluate the accuracy of the analytical method.The exposure amounts of various matrices were calculated from extraction volume and concentration of the target compound. The dermal exposure to chlorantraniliprole was 0.6 mg [0.001% of the total active ingredient (a.i.)] for mixing and loading, and 28.6 mg (0.066% of the total a.i.) for application. The inhalation exposure to chlorantraniliprole was 7.2 μg (1.3%, 1.2 × 10The risk assessment results demonstrated that the risk of chlorantraniliprole exposure in rice paddies was low during application than during mixing and loading. © 2022 Society of Chemical Industry.

Although mesoporous silica nanoparticles (MSNs) are widely used as anticancer drug carriers, unmodified MSNs induce off-target effects and at high doses, there are adverse effects of hemolysis because of the interaction with the silanol group on the surface and cells. In this study, we developed doxorubicin (DOX)-loaded MSNs coated with mannose grafted poly (acrylic acid) copolymer (DOX@MSNs-man-g-PAA) to enhance the hemocompatibility and target efficacy to cancer cells. This uniform nanosized DOX@MSNs-man-g-PAA showed sustained and pH-dependent drug release with improved hemocompatibility over the bare MSNs. The uptake of the DOX@MSN-man-g-PAA in breast cancer cells was significantly improved by mannose receptor-mediated endocytosis, which showed significant increasing intracellular ROS and changes in mitochondrial membrane potential. This formulation exhibited superior tumor-suppressing activity in the MDA-MB-231 cells inoculated mice. Overall, the present study suggested the possibility of the copolymer-coated MSNs as drug carriers for cancer therapy.

Ticagrelor (TCG), an antiplatelet agent, has low solubility and permeability; thus, there are many trials to apply the pharmaceutical technology for the enhancement of TCG solubility and permeability. Herein, we have developed the TCG high-loaded nanostructured lipid carrier (HL-NLC) and solidified the HL-NLC to develop the oral tablet. The HL-NLC was successfully fabricated and optimized with a particle size of 164.5 nm, a PDI of 0.199, an encapsulation efficiency of 98.5%, and a drug loading of 16.4%. For the solidification of HL-NLC (S-HL-NLC), the adsorbent was determined based on the physical properties of the S-HL-NLC, such as bulk density, tap density, angle of repose, Hausner ratio, Carr's index, and drug content. Florite R was chosen because of its excellent adsorption capacity, excellent physical properties, and solubility of the powder after manufacturing. Using an S-HL-NLC, the S-HL-NLC tablet with HPMC 4 K was prepared, which is showed a released extent of more than 90% at 24 h. Thus, we have developed the sustained release tablet containing the TCG-loaded HL-NLC. Moreover, the formulations have exhibited no cytotoxicity against Caco-2 cells and improved the cellular uptake of TCG. In pharmacokinetic study, compared with raw TCG, the bioavailability of HL-NLC and S-HL-NLC was increased by 293% and 323%, respectively. In conclusion, we successfully developed the TCG high-loaded NLC tablet, that exhibited a sustained release profile and enhanced oral bioavailability.

How could queer activism for social change be possible in an authoritarian but neoliberal environment? What does neoliberalism imply for queer struggles in non-Western contexts where liberal democracy is absent or non-existent? This article introduces the concept of ‘quiet politics’ to establish a new theoretical lens for understanding queer organizing under global capitalism. Drawing on ethnographic fieldwork and interview data on the rise of corporate diversity activism in Singapore, it analyzes how queer employees navigate the contradictions of neoliberal capitalism in multinational corporations. The concept of quiet politics helps us understand the nuanced ways in which queer subjects ‘quietly’ mobilize themselves through a negotiation of neoliberalism, queer politics, and the authoritarian government that persecutes homosexuality. In doing so, this article challenges the Western notion of queer liberalism and sheds new light on the complex entanglement of neoliberal capitalism, corporate diversity, contentious politics, and queer activism from a global perspective.

We probed the lifecycle of Epstein-Barr virus (EBV) on a cell-by-cell basis using single cell RNA sequencing (scRNA-seq) data from nine publicly available lymphoblastoid cell lines (LCLs). While the majority of LCLs comprised cells containing EBV in the latent phase, two other clusters of cells were clearly evident and were distinguished by distinct expression of host and viral genes. Notably, both were high expressors of EBV LMP1/BNLF2 and BZLF1 compared to another cluster that expressed neither gene. The two novel clusters differed from each other in their expression of EBV lytic genes, including glycoprotein gene GP350. The first cluster, comprising GP350

Microneedles (MNs), one of the transdermal drug delivery systems, have received extensive interest as an alternative to parenteral or parenteral administrations. For the successful drug delivery of coated MNs, the coated drug or chemical of MNs should be dissolved by skin's interstitial fluid and completely released from the MNs. Thus, the rapid disintegration of the drug from MNs plays a crucial role in ideal drug delivery of MNs. In this study, we developed the rapid disintegration coating formulation to reduce the application time of MN. The rapid disintegration MN was developed using polymers (PVA or HPMC), glycerol, croscarmellose sodium, tween 80, and Brij, as thickener, plasticizer, disintegrating agent, and surfactants, respectively. HPMC MN showed the burst release and rapid disintegration. Moreover, the drug from HPMC MN was successfully delivered into porcine skin within 1 min. In toxicological evaluation, the HPMC MN did not alter the liver and kidney function. Besides, HPMC MN did not induce the acute inflammation and change of skin structure after the application on rat skin. Thus, the coating formulation in this study could be one of the options for the development of safe and rapid disintegration MN.

We probed the lifecycle of EBV on a cell-by-cell basis using single cell RNA sequencing (scRNA-seq) data from nine publicly available lymphoblastoid cell lines (LCL). While the majority of LCLs comprised cells containing EBV in the latent phase, two other clusters of cells were clearly evident and were distinguished by distinct expression of host and viral genes. Notably, both were high expressors of EBV LMP1/BNLF2 and BZLF1 compared to another cluster that expressed neither gene. The two novel clusters differed from each other in their expression of EBV lytic genes, including glycoprotein gene GP350. The first cluster, comprising GP350−LMP1hi cells, expressed high levels of HIF1A and was transcriptionally regulated by HIF1-α. Treatment of LCLs with Pevonedistat, a drug that enhances HIF1-α signaling, markedly induced this cluster. The second cluster, containing GP350+LMP1hi cells, expressed EBV lytic genes. Host genes that are controlled by super-enhancers (SEs), such as transcription factors MYC and IRF4, had the lowest expression in this cluster. Functionally, the expression of genes regulated by MYC and IRF4 in GP350+LMP1hi cells were lower compared to other cells. Indeed, induction of EBV lytic reactivation in EBV+ AKATA reduced the expression of these SE-regulated genes. Furthermore, CRISPR-mediated perturbation of the MYC or IRF4 SEs in LCLs induced the lytic EBV gene expression, suggesting that host SEs and/or SE target genes are required for maintenance of EBV latency. Collectively, our study revealed EBV associated heterogeneity among LCLs that may have functional consequence on host and viral biology.ImportanceEpstein-Barr virus (EBV) establishes a life-long latency program within host cells. As such, EBV immortalized lymphoblastoid cells (LCLs) often carry the latent EBV genome and only a small percentage of LCLs containing lytic EBV. However, the cellular programs that distinguish latent from lytic cells and the heterogeneity of cells in latent or lytic phases remains poorly explored. To explore these unknowns, we reanalyzed publicly available single cell RNA-seq data from nine LCLs. This approach permitted the simultaneous study of cells in both latent and lytic phases. We identified three cell populations with distinct lytic/latent activity and further characterized the transcriptomes of these cells. We also identified a new role of super-enhancers in regulating EBV lytic replication. Collectively, our studies revealed EBV associated heterogeneity among LCLs that contribute to EBV life cycle and biology.

We report on a small-size light detection and ranging (LiDAR) sensor, which offers the possibility of being used in the field during oil spill incidents. In the present study, we develop an algorithm that can distinguish between seawater and oil through the use of a laser at 905 nm wavelength. We investigate the ability of the sensor to detect three different oil types (light crude, bunker A, and bunker C) through experiments and analyze the differences between the types and volumes of spilled oil (1, 5, 10, 15, 20, 25, 30, 35, 40, and 50 mL). The results showed that our algorithm for detecting oil spills over seawater was successful: the LiDAR sensor was able to detect different oil types and volumes. Spilled oil area coverage ranged by more than 50% of the detected area, and the viscosity of bunker C oil reached up to 73%. In addition, the experimental oil spills were mainly formed of oil films of 1 mm and 2 mm thicknesses, which confirmed geometrical properties. Follow-up research should further investigate the characteristics of oil slick thickness measured by the LiDAR system and undertake field tests to assess the feasibility of using the LiDAR system in pollution incidents.

Zaltoprofen is a nonsteroidal anti-inflammatory drug with poor oral bioavailability. S(+)-zaltoprofen (SZPF)-loaded nanostructured lipid carriers (NLCs) were prepared to enhance oral bioavailability. SZPF-loaded NLCs (NLC-SZPF) were prepared using the hot-melting homogenization method and optimized using the Box-Behnken design. The characterization of optimized NLC-SZPF, in vitro release, cytotoxicity, cellular uptake, ex vivo permeability, and pharmacokinetic parameters were evaluated to confirm the advantages of NLC formulation. NLC-SZPF with a diameter of 105.5 ± 1.2 nm had a high encapsulation efficiency of 99.84 ± 0.01%. NLC-SZPF showed a sustained-release profile, high biocompatibility, and high permeability across the intestinal tract. The relative bioavailability of NLC-SZPF was 431.3% compared with that of SZPF after oral administration to experimental rats. NLC-SZPF was successfully optimized using experimental designs to enhance the oral bioavailability of SZPF. Hence, NLC-SZPF could be a promising approach to overcome the poor oral bioavailability of SZPF.