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Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), a deadly disease with limited preventive strategies. Lifestyle interventions to decrease obesity represent a potential approach to prevent obesity-associated PDAC. In this study, we examined whether decreasing obesity through physical activity (PA) and/or dietary changes could decrease inflammation in humans and prevent obesity-associated PDAC in mice. Comparison of circulating inflammatory-associated cytokines in subjects (overweight and obese) before and after a PA intervention revealed PA lowered systemic inflammatory cytokines. Mice with pancreatic-specific inducible KrasG12D expression were exposed to PA and/or dietary interventions during and after obesity-associated cancer initiation. In mice with concurrent diet-induced obesity and KrasG12D expression, the PA intervention led to lower weight gain, suppressed systemic inflammation, delayed tumor progression, and decreased proinflammatory signals in the adipose tissue. However, these benefits were not as evident when obesity preceded pancreatic KrasG12D expression. Combining PA with diet-induced weight loss (DI-WL) delayed obesity-associated PDAC progression in the genetically engineered mouse model, but neither PA alone nor combined with DI-WL or chemotherapy prevented PDAC tumor growth in orthotopic PDAC models regardless of obesity status. PA led to the upregulation of Il15ra in adipose tissue. Adipose-specific overexpression of Il15 slowed PDAC growth but only in nonobese mice. Overall, our study suggests that PA alone or combined with DI-WL can reduce inflammation and delay obesity-associated PDAC development or progression. Lifestyle interventions that prevent or manage obesity or therapies that target weight loss-related molecular pathways could prevent progression of PDAC. Significance: Physical activity reduces inflammation and induces changes to adipose-related signaling to suppress pancreatic cancer, supporting the potential of obesity management strategies to reduce the risk of developing pancreatic cancer. See related commentary by Sogunro and Muzumdar, p. 2935., (©2024 American Association for Cancer Research.)

Inspired by animals with a slippery epidermis, durable slippery antibiofouling coatings with liquid-like wetting buckled surfaces are successfully constructed in this study by combining dynamic-interfacial-release-induced buckling with self-assembled silicon-containing diblock copolymer (diBCP). The core diBCP material is polystyrene- block -poly(dimethylsiloxane) (PS- b -PDMS). Because silicon-containing polymers with intrinsic characters of low surface energy, they easily flow over and cover a surface after it has undergone controlled thermal treatment, generating a slippery wetting layer on which can eliminate polar interactions with biomolecules. Additionally, microbuckled patterns result in curved surfaces, which offer fewer points at which organisms can attach to the surface. Different from traditional slippery liquid-infused porous surfaces, the proposed liquid-like PDMS wetting layer, chemically bonded with PS, is stable and slippery but does not flow away. PS- b -PDMS diBCPs with various PDMS volume fractions are studied to compare the influence of PDMS segment length on antibiofouling performance. The surface characteristics of the diBCPs─ease of processing, transparency, and antibiofouling, anti-icing, and self-cleaning abilities─are examined under various conditions. Being able to fabricate ecofriendly silicon-based lubricant layers without needing to use fluorinated compounds and costly material precursors is an advantage in industrial practice.

The circadian clock is responsible for the regulation of different cellular processes, and its disturbance has been linked to the development of different diseases, such as cancer. The main molecular mechanism for this issue has been linked to the crosstalk between core clock regulators and intracellular pathways responsible for cell survival. The PI3K/AKT signalling pathway is one of the most known intracellular pathways in the case of cancer initiation and progression. This pathway regulates different aspects of cell survival including proliferation, apoptosis, metabolism, and response to environmental stimuli. Accumulating evidence indicates that there is a link between the PI3K/AKT pathway activity and circadian rhythm in physiologic and cancer-related pathogenesis. Different classes of PI3Ks and AKT isoforms are involved in regulating circadian clock components in a transcriptional and functional manner. Reversely, core clock components induce a rhythmic fashion in PI3K and AKT activity in physiologic and pathogenic conditions. The aim of this review is to re-examine the interplay between this pathway and circadian clock components in normal condition and cancer pathogenesis, which provides a better understanding of how circadian rhythms may be involved in cancer progression., (© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Inspired by the superglue fuming method for fingerprint collection, this study developed a novel interfacial-fuming-induced surface instability process to generate wrinkled patterns on polymeric substrates. High-electronegativity groups are introduced on the substrate surface to initiate the polymerization of monomer vapors, such as ethyl cyanoacrylate, which results in the formation of a stiff poly(ethyl cyanoacrylate) capping layer. Moreover, interfacial polymerization resulted in the covalent bonding of the substrate, which led to the volumetric shrinkage of the composite and the accumulation of compressive strain. This process ultimately resulted in the development and stabilization of wrinkled surface morphologies. The authors systematically examined parameters such as the modulus of the epoxy substrate, prestrain, the flow rate of fuming, and operating temperature. The aforementioned technique can be easily applied to architectures with complex outer morphologies and inner surfaces, thereby enabling the construction of surface patterns under ambient conditions without vacuum limitations or precise process control. This study is the first to combine fuming-induced interfacial polymerization with surface instability to create robust wrinkles. The proposed method enables the fabrication of intricate microwrinkled patterns and has considerable potential for use in various practical applications, including microfluidics, optical components, bioinspired adhesive devices, and interfacial engineering., (© 2024 Wiley‐VCH GmbH.)

In this study, a morphological diagram was constructed for quantitatively predicting various modes of surface instabilities caused by the dynamic interfacial release of strain in initially flat bilayer composites comprising an elastomer and a capping layer. Theory, experiment, and simulation were combined to produce the diagram, which enables systematic generation of the following instability patterns: wrinkle, fold, period-double, delamination, and coexisting patterns. The pattern that forms is most strongly affected by three experimental parameters: the elastic modulus of the elastomer, the elastic modulus of the capping layer, and the thickness of the capping layer. The morphological diagram offers understanding of the formation of complex patterns and development of their applications. Critically, the wrinkle alignment can be well controlled by changing the direction of the interfacial release to enable the creation of centimeter-sized and highly ordered lamellar wrinkled patterns with a single orientation on a soft elastomer without the need for costly high-vacuum instruments or complex fabrication processes. The method and diagram have great potential for broad use in many practical applications ranging from flexible electronic devices to smart windows.

The novel coronavirus (COVID-19) pandemic has completely changed our lives and how we interact with the world. The pandemic has brought about a pressing need to have effective disinfection practices that can be incorporated into daily life. They are needed to limit the spread of infections through surfaces and air, particularly in public settings. Most of the current methods utilize chemical disinfectants, which can be laborious and time-consuming. Ultraviolet (UV) irradiation is a proven and powerful means of disinfection. There has been a rising interest in the implementation of UV disinfection robots by various public institutions, such as hospitals, long-term care homes, airports, and shopping malls. The use of UV-based disinfection robots could make the disinfection process faster and more efficient. The objective of this review is to equip readers with the necessary background on UV disinfection and provide relevant discussion on various aspects of UV robots., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier B.V. All rights reserved.)

Ethanol has been shown to suppress essential tremor (ET) in patients at low-to-moderate doses, but its mechanism(s) of action remain unknown. One of the ET hypotheses attributes the ET tremorgenesis to the over-activated firing of inferior olivary neurons, causing synchronic rhythmic firings of cerebellar Purkinje cells. Purkinje cells, however, also receive excitatory inputs from granule cells where the α6 subunit-containing GABA A receptors (α6GABA A Rs) are abundantly expressed. Since ethanol is a positive allosteric modulator (PAM) of α6GABA A Rs, such action may mediate its anti-tremor effect. Employing the harmaline-induced ET model in male ICR mice, we evaluated the possible anti-tremor effects of ethanol and α6GABA A R-selective pyrazoloquinolinone PAMs. The burrowing activity, an indicator of well-being in rodents, was measured concurrently. Ethanol significantly and dose-dependently attenuated action tremor at non-sedative doses (0.4-2.4 g/kg, i.p.). Propranolol and α6GABA A R-selective pyrazoloquinolinones also significantly suppressed tremor activity. Neither ethanol nor propranolol, but only pyrazoloquinolinones, restored burrowing activity in harmaline-treated mice. Importantly, intra-cerebellar micro-injection of furosemide (an α6GABA A R antagonist) had a trend of blocking the effect of pyrazoloquinolinone Compound 6 or ethanol on harmaline-induced tremor. In addition, the anti-tremor effects of Compound 6 and ethanol were synergistic. These results suggest that low doses of ethanol and α6GABA A R-selective PAMs can attenuate action tremor, at least partially by modulating cerebellar α6GABA A Rs. Thus, α6GABA A Rs are potential therapeutic targets for ET, and α6GABA A R-selective PAMs may be a potential mono- or add-on therapy., (© 2023. The American Society for Experimental Neurotherapeutics, Inc.)

Nile tilapia ( Oreochromis niloticus ) is one of the most important food fish in the world. However, the farming industry has encountered significant challenges, such as pathogen infections. Toll-like receptors (TLRs) play an essential role in the initiation of the innate immune system against pathogens. Sterile alpha and TIR motif-containing protein 1 (SARM1) is one of the most evolutionarily conserved TLR adaptors, and its orthologs are present in various species from worms to humans. SARM1 plays an important role in negatively regulating TIR domain-containing adaptor proteins inducing IFNβ (TRIF)-dependent TLR signaling in mammals, but its immune function remains poorly understood in fish. In this study, O. niloticus SARM1 ( OnSARM1 ) was cloned and its evolutionary status was verified using bioinformatic analyses. mRNA expression of OnSARM1 was found at a higher level in the trunk kidney and muscle in healthy fish. The examination of its subcellular location showed that the OnSARM1 was detected only in the cytoplasm of THK cells, and colocalized with OnMyD88, OnTRIF and OnTRIF in small speckle-like condensed granules. The transcript levels of OnMyD88 , OnTIRAP , OnTRIF , and downstream effectors, including interleukin ( IL )- 1β , IL-8 , IL-12b and type I interferon ( IFN ) d2.13 , were regulated conversely to the expression of OnSARM1 in the head kidney from Aeromonas hydrophila and Streptococcus agalactiae infected fish. Moreover, the treatment of THK cells with lysates from A. hydrophila and S. agalactiae enhanced the activity of the NF-κB promoter, but the effects were inhibited in the OnSARM1 overexpressed THK cells. Overexpression of OnSARM1 alone did not activate the NF-κB-luciferase reporter, but it suppressed OnMyD88- and OnTIRAP-mediated NF-κB promoter activity. Additionally, OnSARM1 inhibited the mRNA expression of proinflammatory cytokines and hepcidin in A. hydrophila lysate stimulated THK cells. Taken together, these findings suggest that OnSARM1 serves as a negative regulator by inhibiting NF-κB activity, thereby influencing the transcript level of proinflammatory cytokines and antimicrobial peptides in the antibacterial responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Trung, Nguyen, Hsueh, Loh, Wangkahart, Wong and Lee.)

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer, and the increasing incidence of PDAC may be related to the prevalence of obesity. Physical activity (PA), a method known to mitigate obesity by increasing total energy expenditure, also modifies multiple cellular pathways associated with cancer hallmarks. Epidemiologic evidence has shown that PA can lower the risk of developing a variety of cancers, reduce some of the detrimental side effects of treatments, and improve patient's quality of life during cancer treatment. However, little is known about the pathways underlying the correlations observed between PA interventions and PDAC. Moreover, there is no standard dose of PA intervention that is ideal for PDAC prevention or as an adjuvant of cancer treatments. In this review, we summarize relevant literature showing how PDAC patients can benefit from PA, the potential of PA as an adjuvant treatment for PDAC, the studies using preclinical models of PDAC to study PA, and the clinical trials to date assessing the effects of PA in PDAC., (Copyright © 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.)