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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.

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.

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.

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.sub.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.sub.eq, 5-min) was 60.6 dBA. The adjusted R.sup.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.sup.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.

Hemiparetic gait is one of the most common sequelae of a stroke. Acupuncture has shown potential in correcting hemiplegic gait patterns and improving motor function recovery after stroke. However, controversial findings and a lack of supportive evidence on the effectiveness of acupuncture for post-stroke hemiplegia. The intelligent gait analysis system provides a new perspective for the study of hemiparetic gait. This systematic review aims to collect relevant studies and critically evaluate the efficacy and safety of acupuncture in alleviating gait disturbance of post-stroke hemiplegia based on quantified gait parameters. A comprehensive search of PubMed, Embase, Cochrane stroke group trials register, Cochrane Central Register of Controlled Trials, CINAHL, AMED, three Chinese databases (Chinese Biomedical Literatures database (CBM), National Knowledge Infrastructure (CNKI), and Wan fang Digital Periodicals), four trails registries (The WHO International Clinical Trials Registry Platform, The Chinese Clinical Trial Registry, The US National Institutes of Health Ongoing Trials Register, and The Australian New Zealand Clinical Trials Registry) will be conducted to identify randomised controlled trials of acupuncture for gait disturbance in post-stroke patients. No restrictions on language or publication status. The primary outcomes are gait temporospatial parameters (eg, step length, stride length, step width, step frequency (cadence), walking speed, etc), and gait kinematic parameters (eg, hip peak flex/extend angle, knee peak flex/extend angle, ankle peak dorsi/plantar-flexion angle, etc). We will assess bias using the approach recommended by the Cochrane Handbook for Systematic Reviews of Interventions. A meta-analysis will be conducted to synthesise the evidence for each outcome measure. The χ test and I statistic will be used for assessing heterogeneity between studies. No ethical approval is needed because no primary data is collected. Scientific conferences or peer-reviewed journals will publish the findings. CRD42022384348.

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 BV cells. In addition, we are the first to report that AR inhibition reduced the phagocytotic capability and cell migration of BV 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.

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.

Background This study uses bibliometric analysis to describe the state of research about the association of NO.sub.2, PM.sub.2.5 and noise exposures - three traffic-related pollutants - with cardiometabolic disorders. Methods We retrieved references published 1994-2017 from Scopus and classified references with respect to exposure, health outcome and study design using index keywords. Temporal trend, top cited references, used index keywords and the number of hypothesis testing and non-hypothesis testing study design for each group were identified. Results Results show PM.sub.2.5 is the most frequently studied exposure (47%), followed by both NO.sub.2 and PM.sub.2.5 exposure (29%). Only 3% of references considered multiple exposures between NO.sub.2 and/or PM.sub.2.5 and noise, and these were published after 2008. While we observed a growing trend in studies with NO.sub.2 and/or PM.sub.2.5 and noise and diabetes in the last decade, there is a diminishing trend in studies with noise and diabetes. Different patterns of study designs were found through H/NH ratio, the number of references classified as having a hypothesis (H)-testing design relative to the number of references classified as having a non-hypothesis (NH)-testing design. Studies with NO.sub.2 and/or PM.sub.2.5 exposure are more likely to have a H-testing design, while those with noise exposure are more likely to have a NH-testing design, such as cross-sectional study design. Conclusions We conclude with three themes about research trends. First, the study of simultaneous exposures to multiple pollutants is a current trend, and likely to continue. Second, the association between traffic-related pollutants and diabetes and metabolic symptoms is an area for growth in research. Third, the transition to the use of H-testing study designs to explore associations between noise and cardiometabolic outcomes may be supported by improved understanding of the mechanism of action, and/or improvements to the accuracy and precision of air pollution and noise exposure assessments for environmental health research. Keywords: Bibliometric, Fine particulate matter, PM2.5, Nitrogen dioxide, Multiple, Exposures, Cardiovascular disease, Diabetes, Noise, Cardiometabolic disorders, Study design

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.