In the present study, the effect(s) of the immunomodulatory drug GLS-1027 on various cell types involved in inflammation were investigated. GLS-1027 reduced LPS-stimulated secretion of pro-inflammatory cytokines by macrophage or monocytic cells and cell lines. This reduction was likely due in part to decreased activation of NF-κB family transcription factors and inhibition of p38 MAPK signaling in GLS-1027-treated cells. Independent from its effects on macrophages, GLS-1027 inhibited dendritic cell maturation and differentiation of naïve CD4 + T cells into Th17 cells, reducing the production of typical pro-inflammatory cytokines associated with both processes. In vivo administration of GLS-1027 prevented the development of type 1 diabetes in NOD mice which correlated with reduced serum levels of IL17A in GLS-1027 treated animals and reduced ex vivo production of IL17A from both spleen and lymph-node cells. Overall, our data show that GLS-1027 can reduce inflammation through multiple actions, including the reduction of pro-inflammatory cytokine production by innate immune cells, the inhibition of dendritic cells maturation, and the inhibition of Th17 cells polarization.

SARS-CoV-2 is the third pathogenic coronavirus to emerge since 2000. Experience from prior outbreaks of SARS-CoV and MERS-CoV has demonstrated the importance of both humoral and cellular immunity to clinical outcome, precepts that have been recapitulated for SARS-CoV-2. Despite the unprecedented rapid development and deployment of vaccines against SARS-CoV-2, more vaccines are needed to meet global demand and to guard against immune evasion by newly emerging SARS-CoV-2 variants. Here we describe the development of pGO-1002, a novel bi-cistronic synthetic DNA vaccine that encodes consensus sequences of two SARS-CoV-2 antigens, Spike and ORF3a. Mice immunized with pGO-1002 developed humoral and cellular responses to both antigens, including antibodies and capable of neutralizing infection by a clinical SARS-CoV-2 isolate. Rats immunized with pGO-1002 by intradermal (ID) injection followed by application of suction with our GeneDerm device also developed humoral responses that included neutralizing antibodies and RBD-ACE2 blocking antibodies as well as robust cellular responses to both antigens. Significantly, in a Syrian hamster vaccination and challenge model, ID+GeneDerm-assisted vaccination prevented viral replication in the lungs and significantly reduced viral replication in the nares of hamsters challenged with either an ancestral SARS-CoV-2 strain or the B.1.351 (Beta) variant of concern. Furthermore, vaccinated immune sera inhibited virus-mediated cytopathic effects in vitro. These data establish the immunogenicity of the SARS-CoV-2 vaccine candidate pGO-1002 which induces potent humoral and cellular responses to the Spike and ORF3a antigens and may provide greater protection against emerging variants.

In article number 1900247 by Yan Lee, Tae Hyun Choi, and co-workers, a pH-responsive antibiotic drug conjugate system is developed using a maleic acid amide-based linker. The conjugate system can rapidly release the antibiotics and induce antimicrobial activities against S. aureus at weakly acidic environments in abscesses or inflammatory tissues.

Two representative antibiotics, cephradine (CP) and moxifloxacin (MX), are covalently conjugated with a β‐cyclodextrin (β‐CD)‐based carrier via pH‐responsive 1‐methyl‐2‐(2′‐carboxyethyl) maleic acid amide (MCM) linkers with excellent conjugation efficiency via simple mixing. At pH 5.5, 90% and 80% of the CP and MX, respectively, are released from the carriers within 30 min, in contrast with the much‐delayed release profile at pH 7.4. The in vitro inhibitory effect of β‐CD–MCM–CP on the growth of Staphylococcus aureus is significantly lower than that of free CP at pH 7.4, but it reaches the level of free CP at pH 5.5. Moreover, S. aureus develops significant CP resistance after pretreatment with free CP, whereas the initial CP sensitivity is maintained after pretreatment with β‐CD–MCM–CP at pH 7.4. However, β‐CD–MCM–MX exhibits no such pH‐responsive activity against Bacteroides fragilis , probably due to the insufficient stability of the MX conjugation at pH 7.4. In nondiabetic and diabetic mouse models, β‐CD–MCM–CP significantly reduces the subcutaneous abscess scores and the bacterial counts in the abscess, although this represents only a marginal improvement in antimicrobial activity compared to free CP.

Applications of nano-sized cellulose, such as use in tissue bio-scaffolds and drug delivery, have gained much attention in medical research. However, there are only a few studies reporting the skin toxicity of nano-sized cellulose. Here, we investigated the skin toxicity of plasma-induced nanostructured cellulose (PINC) in vitro and in vivo. Morphology of the PINC as well as that of human foreskin fibroblast (Hs27) and immortalized human keratinocyte (HaCaT) cell lines cultured on PINC were analyzed by scanning electron microscopy. The in vitro cytotoxicity of the material was evaluated using Hs27 and HaCaT cell lines and a reconstructed human epidermis model. For in vivo skin toxicity testing, after attaching the PINC to the dorsal skin of Sprague–Dawley rats, skin irritation was evaluated visually and histologically. Our results showed no cytotoxicity of PINC, which did not induce apoptosis or necrosis in either type of cells tested. PINC also did not stimulate irritation on rats in vivo, and no significant inflammatory responses were observed by histological analysis. These results indicate that PINC has no significant skin toxicity in vitro or in vivo. The absence of skin toxicity in PINC suggests that it can be used for skin-related applications without any harm.

Extremely small amounts of fatty acids detected in latent fingerprints are important for studying fingerprint visualization and age determination through changes in composition over time. However, methods for efficiently extracting or recovering fatty acids from fingerprints have not been extensively studied. If accurate and stable quantitative estimations are established, age estimates will be possible through a better understanding of the fatty acid composition. The extraction solvent and treatment method are essential factors for achieving a reliable analysis of fatty acids. There have been few previous studies that efficiently compared fatty acids. In this study, fatty acids from sebaceous fingerprint residues were quantified with various extraction solvents and treatment methods and were evaluated with gas chromatography flame ionization detection (GC-FID). All data were analyzed using a statistical method.

Background Patient verification by unique identification is an important procedure in health care settings. Risks to patient safety occur throughout health care settings by failure to correctly identify patients, resulting in the incorrect patient, incorrect site procedure, incorrect medication, and other errors. To avoid medical malpractice, radio-frequency identification (RFID), fingerprint scanners, iris scanners, and other technologies have been implemented in care settings. The drawbacks of these technologies include the possibility to lose the RFID bracelet, infection transmission, and impracticality when the patient is unconscious. Objective The purpose of this study was to develop a mobile health app for patient identification to overcome the limitations of current patient identification alternatives. The development of this app is expected to provide an easy-to-use alternative method for patient identification. Methods We have developed a facial recognition mobile app for improved patient verification. As an evaluation purpose, a total of 62 pediatric patients, including both outpatient and inpatient, were registered for the facial recognition test and tracked throughout the facilities for patient verification purpose. Results The app was developed to contain 5 main parts: registration, medical records, examinations, prescriptions, and appointments. Among 62 patients, 30 were outpatients visiting plastic surgery department and 32 were inpatients reserved for surgery. Whether patients were under anesthesia or unconscious, facial recognition verified all patients with 99% accuracy even after a surgery. Conclusions It is possible to correctly identify both outpatients and inpatients and also reduce the unnecessary cost of patient verification by using the mobile facial recognition app with great accuracy. Our mobile app can provide valuable aid to patient verification, including when the patient is unconscious, as an alternative identification method.

Microrobots that are light and agile yet require no artificial power input can be widely used in medical, military, and industrial applications. As an actuation system to drive such robots, here we report a biologically inspired bilayer structure that harnesses the environmental humidity energy, with ratchets to rectify the motion. We named this actuator-ratchet system the hygrobot. The actuator uses a hygroscopically responsive film consisting of aligned nanofibers produced by directional electrospinning, which quickly swells and shrinks in lengthwise direction in response to the change of humidity. The ratchets based on asymmetric friction coefficients rectify oscillatory bending motion in a directional locomotion. We mathematically analyzed the mechanical response of the hygrobot, which allowed not only prediction of its performance but also the optimal design to maximize the locomotion speed given geometric and environmental constraints. The hygrobot sterilized a trail across an agar plate without any artificial energy supply.

ABSTRACT A challenging property of gammaherpesviruses is their ability to establish lifelong persistence. The establishment of latency in B cells is thought to involve active virus engagement of host signaling pathways. Pathogenic effects of these viruses during latency or following reactivation can be devastating to the host. Many cancers, including those associated with members of the gammaherpesvirus family, Kaposi’s sarcoma-associated herpesvirus and Epstein-Barr virus, express elevated levels of active host signal transducer and activator of transcription-3 (STAT3). STAT3 is activated by tyrosine phosphorylation in response to many cytokines and can orchestrate effector responses that include proliferation, inflammation, metastasis, and developmental programming. However, the contribution of STAT3 to gammaherpesvirus pathogenesis remains to be completely understood. This is the first study to have identified STAT3 as a critical host determinant of the ability of gammaherpesvirus to establish long-term latency in an animal model of disease. Following an acute infection, murine gammaherpesvirus 68 (MHV68) established latency in resident B cells, but establishment of latency was dramatically reduced in animals with a B cell-specific STAT3 deletion. The lack of STAT3 in B cells did not impair germinal center responses for immunoglobulin (Ig) class switching in the spleen and did not reduce either total or virus-specific IgG titers. Although ablation of STAT3 in B cells did not have a global effect on these assays of B cell function, it had long-term consequences for the viral load of the host, since virus latency was reduced at 6 to 8 weeks postinfection. Our findings establish host STAT3 as a mediator of gammaherpesvirus persistence. IMPORTANCE The insidious ability of gammaherpesviruses to establish latent infections can have detrimental consequences for the host. Identification of host factors that promote viral latency is essential for understanding latency mechanisms and for therapeutic interventions. We provide the first evidence that STAT3 expression is needed for murine gammaherpesvirus 68 to establish latency in primary B cells during an active immune response to infection. STAT3 deletion in B cells does not impair adaptive immune control of the virus, but loss of STAT3 in B cells has a long-lasting impact on viral persistence. These results indicate a potential therapeutic benefit of STAT3 inhibitors for combating gammaherpesvirus latency and, thereby, associated pathologies.

STAT3 is at the molecular crossroads of innate and adaptive immunity, and in B cells it responds to many cytokines including IL-6, IL-10, and IL-21. We investigated the role of STAT3 in two animal models of disease, the establishment of gammaherpesvirus latency in B cells, and the promotion of B cell lymphomas by the c-myc proto-oncogene. Murine gammaherpesvirus, MHV68, was used to evaluate the requirement of STAT3 for establishment of viral latency in B cells. We infected mice that lacked expression of STAT3 specifically in B cells by both intranasal and intraperitoneal routes. Establishment of viral latency in these animals was substantially impaired compared to controls, as assayed by colonization of the spleen and persistent infection of germinal center immunoglobulin class-switched B cells. There were no dramatic changes in total or virus-specific IgG titers in the absence of B cell STAT3. Our findings recognize STAT3 as a mediator of gammaherpesvirus latency in B cells. The Eμ-myc transgenic mouse is a model of Burkitt’s B cell lymphoma in which elevated levels of c-Myc are expressed in the B cell lineage. We generated Eμ-myc mice that either lacked the IL-6 gene, or lacked the STAT3 gene specifically in B cells to determine the role of the IL-6/STAT3 pathway in tumor development. We found that IL-6 promotes the development of Eμ-myc B cell lymphomas, but the B cell intrinsic expression of STAT3 does not contribute to the development of Eμ-myc lymphomas. Therefore, an IL-6-dependent signal pathway distinct from STAT3 cooperates with Eμ-myc in oncogenesis.

STAT3 responds to cytokines in the microenvironment of the cell to orchestrate effector responses such as proliferation, inflammation, metastasis, and developmental programming. STAT3 is persistently active in many cancers, including those associated with the human gammaherpesvirus pathogens, Kaposi’s sarcoma-associated herpesvirus and Epstein Barr virus. A critical aspect of infection by these viruses is life-long maintenance of the viral genome as a latent episome, commonly in B cells, with the potential for reactivation or cellular transformation. STAT3 is at the molecular crossroads of innate and adaptive immunity, and in B cells it responds to IL-6, IL-10, and IL-21 and promotes high-affinity antibody production. We investigated the role of STAT3 in viral latency establishment in B cells by the murine gammaherpesvirus model pathogen, MHV68, in a newly infected animal. We infected mice with a B cell specific deletion of STAT3 (STAT3fl/fl;CD19-Cre) by intranasal and intraperitoneal routes. Following intranasal infection, establishment of viral latency was substantially impaired as assayed by colonization of the spleen and persistent infection of germinal center immunoglobulin class-switched B cells. The more direct intraperitoneal route allowed infection of germinal center B cells, but still showed a striking defect in latency establishment in class-switched and plasma cells. Regardless of route, persistence of MHV68 was dramatically reduced in the absence of STAT3. The lack of STAT3 did not impact acute infection of lungs, or productive infection in primary fibroblasts in culture, or in vitro reactivation from the few B cell reservoirs in the spleen at 16 dpi. Taken together, we identify STAT3 as a critical host determinant of gammaherpesvirus latency establishment in the animal host. For the first time our findings recognize STAT3 as a mediator of chronic gammaherpesvirus infection in B cells of infected animals, and provide a framework for mechanistic studies of the intrinsic role for STAT3.