Multisensory gamma stimulation mitigates the effects of demyelination induced by cuprizone in male mice.

Demyelination is a common pathological feature in a wide range of diseases, characterized by the loss of myelin sheath and myelin-supporting oligodendrocytes. These losses lead to impaired axonal function, increased vulnerability of axons to damage, and result in significant brain atrophy and neuro-axonal degeneration. Multiple pathomolecular processes contribute to neuroinflammation, oligodendrocyte cell death, and progressive neuronal dysfunction. In this study, we use the cuprizone mouse model of demyelination to investigate long-term non-invasive gamma entrainment using sensory stimulation as a potential therapeutic intervention for promoting myelination and reducing neuroinflammation in male mice. Here, we show that multisensory gamma stimulation mitigates demyelination, promotes oligodendrogenesis, preserves functional integrity and synaptic plasticity, attenuates oligodendrocyte ferroptosis-induced cell death, and reduces brain inflammation. Thus, the protective effects of multisensory gamma stimulation on myelin and anti-neuroinflammatory properties support its potential as a therapeutic approach for demyelinating disorders.

Advanced Mechanical Transfer of Micro-LEDs Enabled by Structurally Modified Wide Sapphire Nanomembranes through Thermal Reflow of Photoresist.

Micro light-emitting diodes (micro-LEDs) are pivotal in next-generation display technologies, driven by the need for high pixel density. This study introduces a novel methodology utilizing wide sapphire nanomembranes (W-SNM) as a dual-purpose template for high-quality epitaxial growth and the mechanical lift-off of individual micro-LEDs. Micro-LEDs grow individually on W-SNM, obviating the chip singulation process. By employing mechanical fracturing of the thin W-SNM, our method facilitates the transfer of micro-LEDs without the conventional laser lift-off (LLO) process. Previously introduced sapphire nanomembranes (SNM) have shown promise in enhancing epitaxial layer quality; however, they encountered challenges in managing micro-LED size variation and achieving efficient mechanical transfer. Here, we apply simple yet effective adjustments to the SNM structure, specifically, its elevation and widening. This strategic modification allows micro-LEDs to endure applied forces without incurring cracks or defects, ensuring that only the targeted W-SNM are selectively fractured. The mechanically transferred vertical 15 × 15 µm2 micro-LED device operates at an optimal turn-on voltage of 3.3 V. Finite element simulations validate the mechanical strain distribution between the W-SNM and GaN when pressure is applied, confirming the efficacy of our design approach. This pioneering methodology offers a streamlined, efficient pathway for the production and mechanical transfer of micro-LEDs, presenting new avenues for their integration into next-generation, high-performance displays.

Adiponectin receptor 1 regulates endometrial receptivity via the adenosine monophosphate­activated protein kinase/E­cadherin pathway.

Endometrial receptivity is essential for successful embryo implantation and pregnancy initiation and is regulated via various signaling pathways. Adiponectin, an important adipokine, may be a potential regulator of reproductive system functions. The aim of the present study was to elucidate the regulatory role of adiponectin receptor 1 (ADIPOR1) in endometrial receptivity. The endometrial receptivity between RL95­2 and AN3CA cell lines was confirmed using an in vitro JAr spheroid attachment model. 293T cells were transfected with control or short hairpin (sh)ADIPOR1 vectors and RL95­2 cells were transduced with lentiviral particles targeting ADIPOR1. Reverse transcription­quantitative PCR and immunoblot assays were also performed. ADIPOR1 was consistently upregulated in the endometrium during the mid­secretory phase compared with that in the proliferative phase and in receptive RL95­2 cells compared with that in non­receptive AN3CA cells. Stable cell lines with diminished ADIPOR1 expression caused by shRNA showed reduced E­cadherin expression and attenuated in vitro endometrial receptivity. ADIPOR1 regulated AMP­activated protein kinase (AMPK) activity in endometrial epithelial cells. Regulation of AMPK activity via dorsomorphin and 5­aminoimidazole­4­carboxamide ribonucleotide affected E­cadherin expression and in vitro endometrial receptivity. The ADIPOR1/AMPK/E­cadherin axis is vital to endometrial receptivity. These findings can help improve fertility treatments and outcomes.

GPx1-ERK1/2-CREB pathway regulates the distinct vulnerability of hippocampal neurons to oxidative stress via modulating mitochondrial dynamics following status epilepticus.

Glutathione peroxidase-1 (GPx1) and cAMP/Ca2+ responsive element (CRE)-binding protein (CREB) regulate neuronal viability by maintaining the redox homeostasis. Since GPx1 and CREB reciprocally regulate each other, it is likely that GPx1-CREB interaction may play a neuroprotective role against oxidative stress, which are largely unknown. Thus, we investigated the underlying mechanisms of the reciprocal regulation between GPx1 and CREB in the male rat hippocampus. Under physiological condition, L-buthionine sulfoximine (BSO)-induced oxidative stress increased GPx1 expression, extracellular signal-regulated kinase 1/2 (ERK1/2) activity and CREB serine (S) 133 phosphorylation in CA1 neurons, but not dentate granule cells (DGC), which were diminished by GPx1 siRNA, U0126 or CREB knockdown. GPx1 knockdown inhibited ERK1/2 and CREB activations induced by BSO. CREB knockdown also decreased the efficacy of BSO on ERK1/2 activation. BSO facilitated dynamin-related protein 1 (DRP1)-mediated mitochondrial fission in CA1 neurons, which abrogated by GPx1 knockdown and U0126. CREB knockdown blunted BSO-induced DRP1 upregulation without affecting DRP1 S616 phosphorylation ratio. Following status epilepticus (SE), GPx1 expression was reduced in CA1 neurons and DGC. SE also decreased CREB activity CA1 neurons, but not DGC. SE degenerated CA1 neurons, but not DGC, accompanied by mitochondrial elongation. These post-SE events were ameliorated by N-acetylcysteine (NAC, an antioxidant), but deteriorated by GPx1 knockdown. These findings indicate that a transient GPx1-ERK1/2-CREB activation may be a defense mechanism to protect hippocampal neurons against oxidative stress via maintenance of proper mitochondrial dynamics.

Enhancing CO2 Transport Across the PEG/PPG-Based Crosslinked Rubbery Polymer Membranes with a Sterically Bulky Carbazole-Based ROMP Comonomer.

A series of poly(ethylene glycol)-block-poly(propylene glycol) (PEG/PPG)- and 5,6-di(9H-carbazol-9-yl)isoindoline-1,3-dione (2CZPImide)-based crosslinked rubbery polymer membranes, denoted as PEG/PPG-2CZPImide (x:y), are prepared from the norbornene-functionalized PEG/PPG oligomer (NB-PEG/PPG-NB) and 2-(bicyclo[2.2.1]hept-5-en-2-ylmethyl)-5,6-di(9H-carbazol-9-yl)isoindoline-1,3-dione (2CZPImide-NB) via ring-opening metathesis polymerization (ROMP). The molar ratio (x:y) of the NB-PEG/PPG-NB (x) to 2CZPImide-NB (y) monomers is varied from 10:1 to 6:1. X-ray diffraction (XRD), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), and pure gas permeability studies reveal that the comonomer 2CZPImide-NB successfully increases the d-spacing among the crystalline PEG/PPG segments, hence enhancing the diffusivity of gases through the membranes. The synthesized membranes exhibit good CO2 separation performance, with CO2 permeabilities ranging from 311.1 to 418.1 Barrer and CO2/N2 and CO2/CH4 selectivities of 39.4-52.0 and 13.4-16.0, respectively, approaching the 2008 Robeson upper bound. Moreover, PEG/PPG-2CZPImide (6:1), displaying optimal CO2 permeability and CO2/N2 and CO2/CH4 selectivities, shows long-term stability against physical aging and plasticization resistance up to 20 days and 10 atm, respectively.

Surgical Treatment of Enlarged Cervical Leiomyoma with Concomitant Uterine Prolapse: A Case Report.

This case report details the surgical treatment of a rare enlarged cervical leiomyoma with uterine prolapse in a 48-year-old woman. She presented to Konyang University Hospital with a palpable vaginal mass, lower abdominal pain, and urinary incontinence. Despite being nulliparous, she had severe chronic constipation due to schizophrenia medication and lived in a health care facility separated from her family. Pelvic examination revealed stage 3 uterine prolapse with a large necrotic cervical leiomyoma. A robot-assisted vaginal hysterectomy followed by sacrocolpopexy was performed using the Da Vinci Xi Surgical System. Histopathology confirmed cervical leiomyoma with squamous metaplasia. At a three-month follow-up, there were no complications, pelvic anatomy was restored, and urinary incontinence improved. Although the patient had a systemic infection due to the necrotic cervical leiomyoma, raising concerns about the increased risk of infection associated with mesh use, she was high-risk for pelvic organ prolapse (POP) recurrence due to her medical history and living situation. Therefore, she underwent concurrent surgeries with pre- and postoperative antibiotic treatment, and recovered without complications. Given that the risk of developing POP increases after a hysterectomy, in high-risk patients, as demonstrated in this case, the concurrent surgical correction of POP may be an effective strategy.

Contrast Enhancement Method Using Region-Based Dynamic Clipping Technique for LWIR-Based Thermal Camera of Night Vision Systems.

In the autonomous driving industry, there is a growing trend to employ long-wave infrared (LWIR)-based uncooled thermal-imaging cameras, capable of robustly collecting data even in extreme environments. Consequently, both industry and academia are actively researching contrast-enhancement techniques to improve the quality of LWIR-based thermal-imaging cameras. However, most research results only showcase experimental outcomes using mass-produced products that already incorporate contrast-enhancement techniques. Put differently, there is a lack of experimental data on contrast enhancement post-non-uniformity (NUC) and temperature compensation (TC) processes, which generate the images seen in the final products. To bridge this gap, we propose a histogram equalization (HE)-based contrast enhancement method that incorporates a region-based clipping technique. Furthermore, we present experimental results on the images obtained after applying NUC and TC processes. We simultaneously conducted visual and qualitative performance evaluations on images acquired after NUC and TC processes. In the visual evaluation, it was confirmed that the proposed method improves image clarity and contrast ratio compared to conventional HE-based methods, even in challenging driving scenarios such as tunnels. In the qualitative evaluation, the proposed method demonstrated upper-middle-class rankings in both image quality and processing speed metrics. Therefore, our proposed method proves to be effective for the essential contrast enhancement process in LWIR-based uncooled thermal-imaging cameras intended for autonomous driving platforms.

Dynamic Analysis of the Locomotion Mechanism in Foxtail Robots: Frictional Anisotropy and Bristle Diversity.

This study investigated the locomotion mechanism of foxtail robots, focusing on the frictional anisotropy of tilted bristles under the same friction coefficient and propulsion strategy using bristle diversity. Through dynamic analysis and simulations, we confirmed the frictional anisotropy of tilted bristles and elucidated the role of bristle diversity in generating propulsive force. The interaction between contact nonuniformity and frictional anisotropy was identified as the core principle enabling foxtail locomotion. Simulations of foxtail robots with multiple bristles demonstrated that variations in bristle length, angle, and deformation contribute to propulsive force generation and environmental adaptability. In addition, this study analyzed the influence of major design parameters on frictional anisotropy, highlighting the critical roles of body height, bristle length, stiffness, reference angle, and friction coefficient. The proposed guidelines for designing foxtail robots emphasize securing bristle nonuniformity and inducing contact nonuniformity. The simulation framework presented enables the quantitative prediction and optimization of foxtail robot performance. This research provides valuable insights into foxtail robot locomotion and lays a foundation for the development of efficient and adaptive next-generation robots for diverse environments.

Stretchable OLEDs based on a hidden active area for high fill factor and resolution compensation.

Stretchable organic light-emitting diodes (OLEDs) have emerged as promising optoelectronic devices with exceptional degree of freedom in form factors. However, stretching OLEDs often results in a reduction in the geometrical fill factor (FF), that is the ratio of an active area to the total area, thereby limiting their potential for a broad range of applications. To overcome these challenges, we propose a three-dimensional (3D) architecture adopting a hidden active area that serves a dual role as both an emitting area and an interconnector. For this purpose, an ultrathin OLED is first attached to a 3D rigid island array structure through quadaxial stretching for precise, deformation-free alignment. A portion of the ultrathin OLED is concealed by letting it 'fold in' between the adjacent islands in the initial, non-stretched condition and gradually surfaces to the top upon stretching. This design enables the proposed stretchable OLEDs to exhibit a relatively high FF not only in the initial state but also after substantial deformation corresponding to a 30% biaxial system strain. Moreover, passive-matrix OLED displays that utilize this architecture are shown to be configurable for compensation of post-stretch resolution loss, demonstrating the efficacy of the proposed approach in realizing the full potential of stretchable OLEDs.

The efficacy and safety of leucine-enriched essential amino acids in knee osteoarthritis patients: A randomized controlled trial.

BACKGROUND: Supplementation with leucine-enriched essential amino acids (LEAAs) has shown efficacy in the recovery of muscle injury and activation of muscle synthesis. Muscle function in knee osteoarthritis is a crucial factor for managing pain and preserving ambulatory function. However, the efficacy and safety of LEAAs supplementation in patients with knee osteoarthritis have not been evaluated. METHODS: In this prospective analysis, we evaluated the efficacy and safety of supplementation with 12 g of LEAAs daily for 8 weeks in knee-symptomatic osteoarthritis patients. For assessing the efficacy, clinical pain, calf circumference, and disability were assessed using questionnaires (visual analog scale, Knee Society Score, and 36-item short form survey [SF-36]), laboratory analyses (total protein and albumin), and radiologic study (dual-energy X-ray absorptiometry [DEXA]) for muscle and bone density. To evaluate safety, generalized or localized protein allergic reactions, complete blood count, liver and kidney function, and serum glucose were measured. RESULTS: Sixty-five participants, categorized into the experimental (n = 32) and control (n = 33) groups, were included in this 8-week trial from March 2022 to July 2022. A significantly higher efficacy was observed in the experimental group than in the control group, as indicated by muscle density in the DEXA scan (P = .001) and SF-36 (P < .001). The safety evaluation revealed no related generalized or local protein allergy. Hematological findings, serum glucose, and kidney and liver toxicity were not significantly different between the groups. CONCLUSION: Supplementation with leucine-enriched proteins is safe and efficacious in the improvement of muscle density and quality of life.

A synergistic therapy against influenza virus A/H1N1/PR8 by a HA1 specific neutralizing single-domain VL and an RNA hydrolyzing scFv.

The emergence of anti-influenza drug-resistant strains poses a challenge for influenza therapy due to mutations in the virus's surface protein. Recently, there has been increasing interest in combination therapy consisting of two or more drugs as a potential alternative approach, aiming to enhance therapeutic efficacy. In this study, we investigated a novel synergistic therapy with a vertical effect using a single-domain VL-HA1-specific antibody against H1N1/PR8 and a horizontal effect using an RNA catalytic antibody with broad-spectrum influenza antiviral drug. We isolated a single-domain VL-HA1-specific (NVLH8) antibody binding to the virus particles showing a neutralizing activity against influenza virus A, specifically H1N1/PR8, as determined by the reduction in plaque number and lower viral HA protein expression in vitro. The neutralizing antibody likely prevented the viral entry, specifically at the viral genome-releasing step. Additionally, the 3D8 scFv hydrolyzed viral RNAs in the cytoplasm, including mRNA, vRNA, and cRNA in MDCK cells. The combined treatment of neutralizing antibodies for a vertical effect and 3D8 scFv for a horizontal effect produced a synergistic effect providing a novel approach against viral diseases when compared with a single treatment. Our results indicated that combining treatment, in particular two proteins exhibiting different mechanisms of action increased the antiviral activity against the influenza virus.

Brightening deep-blue perovskite light-emitting diodes: A path to Rec. 2020.

Deep-blue perovskite light-emitting diodes (PeLEDs) of high purity are highly sought after for next-generation displays complying with the Rec. 2020 standard. However, mixed-halide perovskite materials designed for deep-blue emitters are prone to halide vacancies, which readily occur because of the low formation energy of chloride vacancies. This degrades bandgap instability and performance. Here, we propose a chloride vacancy-targeting passivation strategy using sulfonate ligands with different chain lengths. The sulfonate groups have a strong affinity for lead(II) ions, effectively neutralizing vacancies. Our strategy successfully suppressed phase segregation, yielding color-stable deep-blue PeLEDs with an emission peak at 461 nanometers and a maximum luminance (Lmax) of 2707 candela per square meter with external quantum efficiency (EQE) of 3.05%, one of the highest for Rec. 2020 standard-compliant deep-blue PeLEDs. We also observed a notable increase in EQE up to 5.68% at Lmax of 1978 candela per square meter with an emission peak at 461 nanometers by changing the carbon chain length.

Dynamic Occupancy Grid Map with Semantic Information Using Deep Learning-Based BEVFusion Method with Camera and LiDAR Fusion.

In the field of robotics and autonomous driving, dynamic occupancy grid maps (DOGMs) are typically used to represent the position and velocity information of objects. Although three-dimensional light detection and ranging (LiDAR) sensor-based DOGMs have been actively researched, they have limitations, as they cannot classify types of objects. Therefore, in this study, a deep learning-based camera-LiDAR sensor fusion technique is employed as input to DOGMs. Consequently, not only the position and velocity information of objects but also their class information can be updated, expanding the application areas of DOGMs. Moreover, unclassified LiDAR point measurements contribute to the formation of a map of the surrounding environment, improving the reliability of perception by registering objects that were not classified by deep learning. To achieve this, we developed update rules on the basis of the Dempster-Shafer evidence theory, incorporating class information and the uncertainty of objects occupying grid cells. Furthermore, we analyzed the accuracy of the velocity estimation using two update models. One assigns the occupancy probability only to the edges of the oriented bounding box, whereas the other assigns the occupancy probability to the entire area of the box. The performance of the developed perception technique is evaluated using the public nuScenes dataset. The developed DOGM with object class information will help autonomous vehicles to navigate in complex urban driving environments by providing them with rich information, such as the class and velocity of nearby obstacles.

Experimental realization of entangled coherent states in two-dimensional harmonic oscillators of a trapped ion.

Entangled coherent states play pivotal roles in various fields such as quantum computation, quantum communication, and quantum sensing. We experimentally demonstrate the generation of entangled coherent states with the two-dimensional motion of a trapped ion system. Using Raman transitions with appropriate detunings, we simultaneously drive the red and blue sidebands of the two transverse axes of a single trapped ion and observe multi-periodic entanglement and disentanglement of its spin and two-dimensional motion. Then, by measuring the spin state, we herald entangled coherent states of the transverse motions of the trapped ion and observe the corresponding modulation in the parity of the phonon distribution of one of the harmonic oscillators. Lastly, we trap two ions in a linear chain and realize Mølmer-Sørensen gate using two-dimensional motion.

Gamma entrainment using audiovisual stimuli alleviates chemobrain pathology and cognitive impairment induced by chemotherapy in mice.

Patients with cancer undergoing chemotherapy frequently experience a neurological condition known as chemotherapy-related cognitive impairment, or "chemobrain," which can persist for the remainder of their lives. Despite the growing prevalence of chemobrain, both its underlying mechanisms and treatment strategies remain poorly understood. Recent findings suggest that chemobrain shares several characteristics with neurodegenerative diseases, including chronic neuroinflammation, DNA damage, and synaptic loss. We investigated whether a noninvasive sensory stimulation treatment we term gamma entrainment using sensory stimuli (GENUS), which has been shown to alleviate aberrant immune and synaptic pathologies in mouse models of neurodegeneration, could also mitigate chemobrain phenotypes in mice administered a chemotherapeutic drug. When administered concurrently with the chemotherapeutic agent cisplatin, GENUS alleviated cisplatin-induced brain pathology, promoted oligodendrocyte survival, and improved cognitive function in a mouse model of chemobrain. These effects persisted for up to 105 days after GENUS treatment, suggesting the potential for long-lasting benefits. However, when administered to mice 90 days after chemotherapy, GENUS treatment only provided limited benefits, indicating that it was most effective when used to prevent the progression of chemobrain pathology. Furthermore, we demonstrated that the effects of GENUS in mice were not limited to cisplatin-induced chemobrain but also extended to methotrexate-induced chemobrain. Collectively, these findings suggest that GENUS may represent a versatile approach for treating chemobrain induced by different chemotherapy agents.

Highly stable and immunogenic CMV T cell vaccine candidate developed using a synthetic MVA platform.

Human cytomegalovirus (CMV) is the most common infectious cause of complications post-transplantation, while a CMV vaccine for transplant recipients has yet to be licensed. Triplex, a multiantigen Modified Vaccinia Ankara (MVA)-vectored CMV vaccine candidate based on the immunodominant antigens phosphoprotein 65 (pp65) and immediate-early 1 and 2 (IE1/2), is in an advanced stage of clinical development. However, its limited genetic and expression stability restricts its potential for large-scale production. Using a recently developed fully synthetic MVA (sMVA) platform, we developed a new generation Triplex vaccine candidate, T10-F10, with different sequence modifications for enhanced vaccine stability. T10-F10 demonstrated genetic and expression stability during extensive virus passaging. In addition, we show that T10-F10 confers comparable immunogenicity to the original Triplex vaccine to elicit antigen-specific T cell responses in HLA-transgenic mice. These results demonstrate improvements in translational vaccine properties of an sMVA-based CMV vaccine candidate designed as a therapeutic treatment for transplant recipients.

Multisensory gamma stimulation promotes glymphatic clearance of amyloid.

The glymphatic movement of fluid through the brain removes metabolic waste1-4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease5-8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer's disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.

Major clinical research advances in gynecologic cancer in 2023: a tumultuous year for endometrial cancer.

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.

Synthetic modified vaccinia Ankara vaccines confer cross-reactive and protective immunity against mpox virus.

BACKGROUND: Although the mpox global health emergency caused by mpox virus (MPXV) clade IIb.1 has ended, mpox cases are still reported due to low vaccination coverage and waning immunity. COH04S1 is a clinically evaluated, multiantigen COVID-19 vaccine candidate built on a fully synthetic platform of the highly attenuated modified vaccinia Ankara (MVA) vector, representing the only FDA-approved smallpox/mpox vaccine JYNNEOS. Given the potential threat of MPXV resurgence and need for vaccine alternatives, we aimed to assess the capacity COH04S1 and its synthetic MVA (sMVA) backbone to confer MPXV-specific immunity. METHODS: We evaluated orthopoxvirus-specific and MPXV cross-reactive immune responses in samples collected during a Phase 1 clinical trial of COH04S1 and in non-human primates (NHP) vaccinated with COH04S1 or its sMVA backbone. MPXV cross-reactive immune responses in COH04S1-vaccinated healthy adults were compared to responses measured in healthy subjects vaccinated with JYNNEOS. Additionally, we evaluated the protective efficacy of COH04S1 and sMVA against mpox in mpox-susceptible CAST/EiJ mice. RESULTS: COH04S1-vaccinated individuals develop robust orthopoxvirus-specific humoral and cellular responses, including cross-reactive antibodies to MPXV-specific virion proteins as well as MPXV cross-neutralizing antibodies in 45% of the subjects. In addition, NHP vaccinated with COH04S1 or sMVA show similar MPXV cross-reactive antibody responses. Moreover, MPXV cross-reactive humoral responses elicited by COH04S1 are comparable to those measured in JYNNEOS-vaccinated subjects. Finally, we show that mice vaccinated with COH04S1 or sMVA are protected from lung infection following challenge with MPXV clade IIb.1. CONCLUSIONS: These results demonstrate the capacity of sMVA vaccines to elicit cross-reactive and protective orthopox-specific immunity against MPXV, suggesting that COH04S1 and sMVA could be developed as bivalent or monovalent mpox vaccine alternatives against MPXV.

Mpox is an ilness caused by the mpox virus (MPXV) that belongs to the poxvirus family. The 2022-2023 mpox outbreak highlights the need to develop effective vaccines against MPXV. We have developed a COVID-19 vaccine using as scaffold chemically synthesized genetic material of a highly attenuated and safe poxvirus vector. This scaffold is the same present in a vaccine that has been approved and is given to prevent mpox. Here, we show that healthy human volunteers or monkeys vaccinated with this COVID-19 vaccine generated a robust immune response against MPXV, similar to that generated by the mpox vaccine with the same scaffold. This COVID-19 vaccine is also able to protect mice from infection caused by the MPXV strain isolated from the recent mpox outbreak. This COVID-19 vaccine in a poxvirus scaffold might be an additional tool to curtail mpox outbreaks.

Skin microbe-dependent TSLP-ILC2 priming axis in early life is co-opted in allergic inflammation.

Although early life colonization of commensal microbes contributes to long-lasting immune imprinting in host tissues, little is known regarding the pathophysiological consequences of postnatal microbial tuning of cutaneous immunity. Here, we show that postnatal exposure to specific skin commensal Staphylococcus lentus (S. lentus) promotes the extent of atopic dermatitis (AD)-like inflammation in adults through priming of group 2 innate lymphoid cells (ILC2s). Early postnatal skin is dynamically populated by discrete subset of primed ILC2s driven by microbiota-dependent induction of thymic stromal lymphopoietin (TSLP) in keratinocytes. Specifically, the indole-3-aldehyde-producing tryptophan metabolic pathway, shared across Staphylococcus species, is involved in TSLP-mediated ILC2 priming. Furthermore, we demonstrate a critical contribution of the early postnatal S. lentus-TSLP-ILC2 priming axis in facilitating AD-like inflammation that is not replicated by later microbial exposure. Thus, our findings highlight the fundamental role of time-dependent neonatal microbial-skin crosstalk in shaping the threshold of innate type 2 immunity co-opted in adulthood.