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Goal-directed navigation requires the hippocampus to process spatial information in a value-dependent manner, but its underlying mechanism needs to be better understood. Here, we investigated whether the dorsal (dHP) and intermediate (iHP) regions of the hippocampus differentially function in processing place and its associated value information. Rats were trained in a place-preference task involving reward zones with different values in a visually rich virtual reality environment where two-dimensional navigation was possible. Rats learned to use distal visual scenes effectively to navigate to the reward zone associated with a higher reward. Inactivation of both dHP and iHP with muscimol altered the efficiency and precision of wayfinding behavior, but iHP inactivation induced more severe damage, including impaired place preference. Our findings suggest that the iHP is more critical for value-dependent navigation toward higher-value goal locations.

Polymeric materials have been used to realize optical systems that, through periodic variations of their structural or optical properties, interact with light-generating holographic signals. Complex holographic systems can also be dynamically controlled through exposure to external stimuli, yet they usually contain only a single type of holographic mode. Here, we report a conjugated organogel that reversibly displays three modes of holograms in a single architecture. Using dithering mask lithography, we realized two-dimensional patterns with varying cross-linking densities on a conjugated polydiacetylene. In protic solvents, the organogel contracts anisotropically to develop optical and structural heterogeneities along the third dimension, displaying holograms in the form of three-dimensional full parallax signals, both in fluorescence and bright-field microscopy imaging. In aprotic solvents, these heterogeneities diminish as organogels expand, recovering the two-dimensional periodicity to display a third hologram mode based on iridescent structural colours. Our study presents a next-generation hologram manufacturing method for multilevel encryption technologies. Periodic patterns with varying cross-linking densities are realized in conjugated polydiacetylene films, creating multiple holographic images—all dynamically responsive to exposure to various solvents—simultaneously in the same polymeric structures.

Goal-directed navigation requires the hippocampus to process spatial information in a value-dependent manner, but its underlying mechanism needs to be better understood. Here, we investigated whether the dorsal (dHP) and intermediate (iHP) regions of the hippocampus differentially function in processing place and its associated value information. Rats were trained in a place-preference task involving reward zones with different values in a visually rich virtual reality environment where two-dimensional navigation was possible. Rats learned to use distal visual scenes effectively to navigate to the reward zone associated with a higher reward. Inactivation of both dHP and iHP with muscimol altered the efficiency and precision of wayfinding behavior, but iHP inactivation induced more severe damage, including impaired place preference. Our findings suggest that the iHP is more critical for value-dependent navigation toward higher-value goal locations.

Goal-directed navigation requires the hippocampus to process spatial information in a value-dependent manner, but its underlying mechanism needs to be better understood. Here, we investigated whether the dorsal (dHP) and intermediate (iHP) regions of the hippocampus differentially function in processing place and its associated value information. Rats were trained in a place-preference task involving reward zones with different values in a visually rich VR environment where two-dimensional navigation was possible. Rats learned to use distal visual scenes effectively to navigate to the reward zone associated with a higher reward. Inactivation of the dHP or iHP with muscimol altered navigational patterns differentially. Specifically, measurements of the efficiency and accuracy of wayfinding behavior using directional analysis showed that iHP inactivation induced more severe damage to value-dependent navigation than dHP inactivation. Our findings suggest that the dHP is more critical for accurate spatial navigation to the target location per se, whereas the iHP is critical for finding higher-value goal locations.Competing Interest StatementThe authors have declared no competing interest.

Hyperimmunity drives the development of Alzheimer disease (AD). The immune system is under the circadian control, and circadian abnormalities aggravate AD progress. Here, we investigate how an AD-linked mutation deregulates expression of circadian genes and induces cognitive decline using the knock-in (KI) mice heterozygous for presenilin 2 N141I mutation. This mutation causes selective overproduction of clock gene-controlled cytokines through the DNA hypermethylation-mediated repression of REV-ERBα in innate immune cells. The KI/+ mice are vulnerable to otherwise innocuous, mild immune challenges. The antipsychotic chlorpromazine restores the REV-ERBα level by normalizing DNA methylation through the inhibition of PI3K/AKT1 pathway, and prevents the overexcitation of innate immune cells and cognitive decline in KI/+ mice. These results highlight a pathogenic link between this AD mutation and immune cell overactivation through the epigenetic suppression of REV-ERBα. Hyperimmunity is associated with Alzheimer disease. Here the authors show that the Presenilin 2 N141I mutation causes overproduction of clock-controlled cytokines and memory deficits through suppression of REV-ERBα gene by hypermethylation.

Microfluidic organ-on-a-chip technologies have enabled construction of biomimetic physiologically and pathologically relevant models. This paper describes an injection molded microfluidic platform that utilizes a novel sequential edge-guided patterning method based on spontaneous capillary flow to realize three-dimensional co-culture models and form an array of micro-vascularized tissues (28 per 1 × 2-inch slide format). The MicroVascular Injection-Molded Plastic Array 3D Culture (MV-IMPACT) platform is fabricated by injection molding, resulting in devices that are reliable and easy to use. By patterning hydrogels containing human umbilical endothelial cells and fibroblasts in close proximity and allowing them to form vasculogenic networks, an array of perfusable vascularized micro-tissues can be formed in a highly efficient manner. The high-throughput generation of angiogenic sprouts was quantified and their uniformity was characterized. Due to its compact design (half the size of a 96-well microtiter plate), it requires small amount of reagents and cells per device. In addition, the device design is compatible with a high content imaging machine such as Yokogawa CQ-1. Furthermore, we demonstrated the potential of our platform for high-throughput phenotypic screening by testing the effect of DAPT, a chemical known to affect angiogenesis. The MV-IMPACT represent a significant improvement over our previous PDMS-based devices in terms of molding 3D co-culture conditions at much higher throughput with added reliability and robustness in obtaining vascular micro-tissues and will provide a platform for developing applications in drug screening and development.

The demand for face masks is increasing exponentially due to the coronavirus pandemic and issues associated with airborne particulate matter (PM). However, both conventional electrostatic‐ and nanosieve‐based mask filters are single‐use and are not degradable or recyclable, which creates serious waste problems. In addition, the former loses function under humid conditions, while the latter operates with a significant air‐pressure drop and suffers from relatively fast pore blockage. Herein, a biodegradable, moisture‐resistant, highly breathable, and high‐performance fibrous mask filter is developed. Briefly, two biodegradable microfiber and nanofiber mats are integrated into a Janus membrane filter and then coated by cationically charged chitosan nanowhiskers. This filter is as efficient as the commercial N95 filter and removes 98.3% of 2.5 µm PM. The nanofiber physically sieves fine PM and the microfiber provides a low pressure differential of 59 Pa, which is comfortable for human breathing. In contrast to the dramatic performance decline of the commercial N95 filter when exposed to moisture, this filter exhibits negligible performance loss and is therefore multi‐usable because the permanent dipoles of the chitosan adsorb ultrafine PM (e.g., nitrogen and sulfur oxides). Importantly, this filter completely decomposes within 4 weeks in composting soil. An eco‐friendly face mask filter with high‐level functionality is developed. Made only of biodegradable materials, it completely decomposes in the soil, thereby providing a fundamental waste problem solution. Moreover, the filter is a practical alternative to conventional disposable filters by integrating the physical sieving role of a poly(butylene succinate) fiber mat and the permanent electrostatic adsorption roles of chitosan nanowhiskers.

Microfluidics offers promising methods for aligning cells in physiologically relevant configurations to recapitulate human organ functionality. Specifically, microstructures within microfluidic devices facilitate 3D cell culture by guiding hydrogel precursors containing cells. Conventional approaches utilize capillary forces of hydrogel precursors to guide fluid flow into desired areas of high wettability. These methods, however, require complicated fabrication processes and subtle loading protocols, thus limiting device throughput and experimental yield. Here, we present a swift and robust hydrogel patterning technique for 3D cell culture, where preloaded hydrogel solution in a microfluidic device is aspirated while only leaving a portion of the solution in desired channels. The device is designed such that differing critical capillary pressure conditions are established over the interfaces of the loaded hydrogel solution, which leads to controlled removal of the solution during aspiration. A proposed theoretical model of capillary pressure conditions provides physical insights to inform generalized design rules for device structures. We demonstrate formation of multiple, discontinuous hollow channels with a single aspiration. Then we test vasculogenic capacity of various cell types using a microfluidic device obtained by our technique to illustrate its capabilities as a viable micro-manufacturing scheme for high-throughput cellular co-culture.

This study aims to figure out the worldwide prevalence of anticancer therapy-associated acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) and the relative risk of each cancer drug. We conducted an analysis of VigiBase, the World Health Organization pharmacovigilance database, 1967–2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) and information component (IC) compares observed and expected values to investigate the associations of each category of anticancer drugs with AKI and TIN. We identified 32,722 and 2056 reports (male, n = 17,829 and 1,293) of anticancer therapy-associated AKI and TIN, respectively, among 4,592,036 reports of all-drug caused AKI and TIN. There has been a significant increase in reports since 2010, primarily due to increased reports of targeted therapy and immunotherapy. Immunotherapy exhibited a significant association with both AKI (ROR: 8.92; IC 0.25 : 3.06) and TIN (21.74; 4.24), followed by cytotoxic therapy (7.14; 2.68), targeted therapy (5.83; 2.40), and hormone therapy (2.59; 1.24) for AKI, and by cytotoxic therapy (2.60; 1.21) and targeted therapy (1.54; 0.61) for TIN. AKI and TIN were more prevalent among individuals under 45 years of age, with a female preponderance for AKI and males for TIN. These events were reported in close temporal relationship after initiation of the respective drug (16.53 days for AKI and 27.97 days for TIN), and exhibited a high fatality rate, with 23.6% for AKI and 16.3% for TIN. These findings underscore that kidney-related adverse drug reactions are of prognostic significance and strategies to mitigate such side effects are required to optimize anticancer therapy.