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ADAM9 (A disintegrin and a metalloprotease 9) is a membrane-anchored protein that participates in a variety of physiological functions, primarily through the disintegrin domain for adhesion and the metalloprotease domain for ectodomain shedding of a wide variety of cell surface proteins. ADAM9 influences the developmental process, inflammation, and degenerative diseases. Recently, increasing evidence has shown that ADAM9 plays an important role in tumor biology. Overexpression of ADAM9 has been found in several cancer types and is correlated with tumor aggressiveness and poor prognosis. In addition, through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies. In this review, we summarize the current understanding of ADAM9 in biological function, pathophysiological diseases, and various cancers. Recent advances in therapeutic strategies using ADAM9-related pathways are presented as well.

Fluorescence correlation spectroscopy (FCS) is an extremely versatile tool that has been widely used to measure chemical reaction rates, protein binding, nanoparticle-protein interactions, and biomolecular dynamics in vitro and in vivo. As an inherently micro-sized approach, FCS is compatible with high-throughput screening applications, as demanded for drug design, but typically limited to nanomolar concentrations, which restricts possible applications. Here, we show how massively parallel camera-based detection with side illumination can extend the usable concentration range of FCS more than 100-fold to measure low affinity processes. Our line illumination (LIM) approach is robust, fast (1 s acquisition times), and does not require any reference measurements to characterize the observation volume size.

We investigate the unintended consequences of carryout grocery bag (CGB) regulations by looking at the impact on sales of alternative plastic bag products. We extend the literature by studying two types of CGB regulations, bag bans and bag fees. Using retail scanner data and employing a general synthetic control method, we find that both types of CGB regulations are associated with significantly higher plastic trash bag sales. We estimate that CGB regulations lead to an average increase in purchased plastics of 127 pounds per store per month, ranging from 30 to 135 (37–224) pounds for 4-gallon (8-gallon) trash bags. These results confirm previous findings on bag bans and provide new evidence on bag fees. In general, the effects do not differ across CGB regulations, but some heterogeneity exists. Our results highlight unintentional spillover effects of narrowly targeted policies on other unregulated waste.

There are an estimated 5.4 million snakebite cases every year. People with snakebite envenoming suffer from severe complications, or even death. Although some review articles cover several topics of snakebite envenoming, a review of the cases regarding cerebral complications, especially rare syndromes, is lacking. Here, we overview 35 cases of snakebite by front-fanged snakes, including Bothrops, Daboia, Cerastes, Deinagkistrodon, Trimeresurus, and Crotalus in the Viperidae family; Bungarus and Naja in the Elapidae family, and Homoroselaps (rare cases) in the Lamprophiidae family. We also review three rare cases of snakebite by rear-fanged snakes, including Oxybelis and Leptodeira in the Colubridae family. In the cases of viper bites, most patients (17/24) were diagnosed with ischemic stroke and intracranial hemorrhage, leading to six deaths. We then discuss the potential underlying molecular mechanisms that cause these complications. In cases of elapid bites, neural, cardiac, and ophthalmic disorders are the main complications. Due to the small amount of venom injection and the inability to deep bite, all the rear-fanged snakebites did not develop any severe complications. To date, antivenom (AV) is the most effective therapy for snakebite envenoming. In the six cases of viper and elapid bites that did not receive AV, three cases (two by viper and one by elapid) resulted in death. This indicates that AV treatment is the key to survival after a venomous snakebite. Lastly, we also discuss several studies of therapeutic agents against snakebite-envenoming-induced complications, which could be potential adjuvants along with AV treatment. This article organizes the diagnosis of hemotoxic and neurotoxic envenoming, which may help ER doctors determine the treatment for unidentified snakebite.

Environmental noise may affect hearing and a variety of non-auditory disease processes. There is some evidence that, like other environmental hazards, noise may be differentially distributed across communities based on socioeconomic status. We aimed to a) predict daytime noise pollution levels and b) assess disparities in daytime noise exposure in Chicago, Illinois. We measured 5-minute daytime noise levels (L eq, 5-min ) at 75 randomly selected sites in Chicago in March, 2019. Geographically-based variables thought to be associated with noise were obtained, and used to fit a noise land-use regression model to estimate the daytime environmental noise level at the centroid of the census blocks. Demographic and socioeconomic data were obtained from the City of Chicago for the 77 community areas, and associations with daytime noise levels were assessed using spatial autoregressive models. Mean sampled noise level (L eq, 5-min ) was 60.6 dBA. The adjusted R 2 and root mean square error of the noise land use regression model and the validation model were 0.60 and 4.67 dBA and 0.51 and 5.90 dBA, respectively. Nearly 75% of city blocks and 85% of city communities have predicted daytime noise level higher than 55 dBA. Of the socioeconomic variables explored, only community per capita income was associated with mean community predicted noise levels, and was highest for communities with incomes in the 2 nd quartile. Both the noise measurements and land-use regression modeling demonstrate that Chicago has levels of environmental noise likely contributing to the total burden of environmental stressors. Noise is not uniformly distributed across Chicago; it is associated with proximity to roads and public transportation, and is higher among communities with mid-to-low incomes per capita, which highlights how socially and economically disadvantaged communities may be disproportionately impacted by this environmental exposure.

The occurrence of Alzheimer’s disease has been associated with the accumulation of beta-amyloid (β-amyloid) plaques. These plaques activate microglia to secrete inflammatory molecules, which damage neurons in the brain. Thus, understanding the underlying mechanism of microglia activation can provide a therapeutic strategy for alleviating microglia-induced neuroinflammation. The aldose reductase (AR) enzyme catalyzes the reduction of glucose to sorbitol in the polyol pathway. In addition to mediating diabetic complications in hyperglycemic environments, AR also helps regulate inflammation in microglia. However, little is known about the role of AR in β-amyloid-induced inflammation in microglia and subsequent neuronal death. In this study, we confirmed that AR inhibition attenuates increased β-amyloid-induced reactive oxygen species and tumor necrosis factor α secretion by suppressing ERK signaling in BV2 cells. In addition, we are the first to report that AR inhibition reduced the phagocytotic capability and cell migration of BV2 cells in response to β-amyloid. To further investigate the protective role of the AR inhibitor sorbinil in neurons, we co-cultured β-amyloid-induced microglia with stem cell-induced neurons. sorbinil ameliorated neuronal damage in both cells in the co-culture system. In summary, our findings reveal AR regulation of microglia activation as a novel therapeutic target for Alzheimer’s disease.

Little is known about the detailed clinical description, pathophysiology, and efficacy of treatments for ocular envenoming (venom ophthalmia) caused by venom of the spitting elapid and other snakes, as well as ocular complications caused by snake venom injection. In this paper, we review clinical information of case reports regarding venom ophthalmia and snake venom injection with associated ocular injuries in Asia, Africa, and the United States. We also review the literature of snake venom such as their compositions, properties, and toxic effects. Based on the available clinical information and animal studies, we further discuss possible mechanisms of venom ophthalmia derived from two different routes (Duvernoy’s gland in the mouth and nuchal gland in the dorsal neck) and the pathophysiology of snake venom injection induced ocular complications, including corneal edema, corneal erosion, cataract, ocular inflammation, retinal hemorrhage, acute angle closure glaucoma, as well as ptosis, diplopia, and photophobia. Finally, we discuss the appropriate first aid and novel strategies for treating venom ophthalmia and snake envenoming.

ObjectivesAtopic dermatitis is a chronic, relapsing, inflammatory skin disease that impacts patients’ quality of life and imposes substantial economic burdens on their families. Acupuncture holds promise as a viable treatment option for atopic dermatitis. This review aimed to evaluate the effect of acupuncture on atopic dermatitis.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, CENTRAL, the China National Knowledge Infrastructure, WanFang and VIP databases were searched through 17 September 2023, together with an updated search on 15 October 2024.Eligibility criteria for selecting studiesWe included randomised controlled trials (RCTs) about acupuncture for atopic dermatitis. The primary outcome was the SCORing Atopic Dermatitis (SCORAD) score. The secondary outcomes were the eczema area and severity index (EASI) score, the visual analogue scale (VAS) score for pruritus, the dermatology life quality index (DLQI) score, serum IgE level and adverse events (AEs).Data extraction and synthesisTwo independent reviewers conducted separate searches of the databases, assessed eligible articles for inclusion and employed the Cochrane Collaboration’s tool for assessing the risk of bias. The analyses were performed using RevMan 5.3 and Stata 13.0 software. The mean difference (MD) with 95% CI was employed to analyse continuous outcomes.ResultsEight studies with 463 participants were included. The meta-analysis indicated significant differences in the SCORAD score (MD=−10.61, 95% CI −17.77 to −3.45, p=0.004), the VAS score for pruritus (MD=−14.71, 95% CI −18.20 to −11.22, p<0.00001) and the DLQI score (MD=−2.37, 95% CI −3.57 to −1.18, p<0.0001), but no significant differences in the EASI score (MD=−3.95, 95% CI −8.35 to 0.45, p=0.08) and the IgE level (MD=−160.22 U/mL, 95% CI −334.13 to 13.68, p=0.07) between treatment and control. The differences in the SCORAD score and the VAS score for pruritus reached minimal clinically important differences. No serious AEs were reported.ConclusionsAcupuncture might be an effective and safe treatment for atopic dermatitis. Due to the limited quantity and quality of the included studies, it is recommended to conduct multicentre, large-scale and high-quality RCTs to further confirm the findings.PROSPERO registration numberCRD42023470643.

As part of the central nervous system (CNS), retinal ganglion cells (RGCs) and their axons are the only neurons in the retina that transmit visual signals from the eye to the brain via the optic nerve (ON). Unfortunately, they do not regenerate upon injury in mammals. In ON trauma, retinal microglia (RMG) become activated, inducing inflammatory responses and resulting in axon degeneration and RGC loss. Since aldose reductase (AR) is an inflammatory response mediator highly expressed in RMG, we investigated if pharmacological inhibition of AR can attenuate ocular inflammation and thereby promote RGC survival and axon regeneration after ON crush (ONC). In vitro, we discovered that Sorbinil, an AR inhibitor, attenuates BV2 microglia activation and migration in the lipopolysaccharide (LPS) and monocyte chemoattractant protein-1 (MCP-1) treatments. In vivo, Sorbinil suppressed ONC-induced Iba1 + microglia/macrophage infiltration in the retina and ON and promoted RGC survival. Moreover, Sorbinil restored RGC function and delayed axon degeneration one week after ONC. RNA sequencing data revealed that Sorbinil protects the retina from ONC-induced degeneration by suppressing inflammatory signaling. In summary, we report the first study demonstrating that AR inhibition transiently protects RGC and axon from degeneration, providing a potential therapeutic strategy for optic neuropathies.

Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro‐electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built‐in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell‐derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long‐term recording. Overall, this technology, termed “mind in vitro” to underscore the computing inspiration, provides an end‐to‐end solution that can be widely deployed due to its affordable (>10× cost reduction) and open‐source nature, catering to the expanding needs of both conventional and unconventional electrophysiology. This article presents an accurate, modular, customizable, and portable in vitro neuron electrophysiology solution that can be easily fabricated, robustly operated, and broadly disseminated. The solution integrates reconfigurable recording platforms, open‐source electronics, and in‐house micro‐electrode arrays. The system's utility is showcased through a comprehensive set of demonstrations involving various culture types and stimulation modalities, concurrent imaging, and long‐term recording.