Sarcopenia, which is characterized by progressive and generalized loss of skeletal muscle mass and strength, has been well described to be associated with numerous poor postoperative outcomes, such ...as increased perioperative mortality, postoperative sepsis, prolonged length of stay, increased cost of care, decreased functional outcome, and poorer oncological outcomes in cancer surgery. Multimodal prehabilitation, as a concept that involves boosting and optimizing the preoperative condition of a patient prior to the upcoming stressors of a surgical procedure, has the purported benefits of reversing the effects of sarcopenia, shortening hospitalization, improving the rate of return to bowel activity, reducing the costs of hospitalization, and improving quality of life. This review aims to present the current literature surrounding the concept of sarcopenia, its implications pertaining to colorectal cancer and surgery, a summary of studied multimodal prehabilitation interventions, and potential future advances in the management of sarcopenia.
Lates calcarifer, known as seabass in Asia and barramundi in Australia, is a widely farmed species internationally and in Southeast Asia and any disease outbreak will have a great economic impact on ...the aquaculture industry. Through disease investigation of Asian seabass from a coastal fish farm in 2015 in Singapore, a novel birnavirus named Lates calcarifer Birnavirus (LCBV) was detected and we sought to isolate and characterize the virus through molecular and biochemical methods.
In order to propagate the novel birnavirus LCBV, the virus was inoculated into the Bluegill Fry (BF-2) cell line and similar clinical signs of disease were reproduced in an experimental fish challenge study using the virus isolate. Virus morphology was visualized using transmission electron microscopy (TEM). Biochemical analysis using chloroform and 5-Bromo-2'-deoxyuridine (BUDR) sensitivity assays were employed to characterize the virus. Next-Generation Sequencing (NGS) was also used to obtain the virus genome for genetic and phylogenetic analyses.
The LCBV-infected BF-2 cell line showed cytopathic effects such as rounding and granulation of cells, localized cell death and detachment of cells observed at 3 to 5 days' post-infection. The propagated virus, when injected intra-peritoneally into naïve Asian seabass under experimental conditions, induced lesions similar to fish naturally infected with LCBV. Morphology of LCBV, visualized under TEM, revealed icosahedral particles around 50 nm in diameter. Chloroform and BUDR sensitivity assays confirmed the virus to be a non-enveloped RNA virus. Further genome analysis using NGS identified the virus to be a birnavirus with two genome segments. Phylogenetic analyses revealed that LCBV is more closely related to the Blosnavirus genus than to the Aquabirnavirus genus within the Birnaviridae family.
These findings revealed the presence of a novel birnavirus that could be linked to the disease observed in the Asian seabass from the coastal fish farms in Singapore. This calls for more studies on disease transmission and enhanced surveillance programs to be carried out to understand pathogenicity and epidemiology of this novel virus. The gene sequences data obtained from the study can also pave way to the development of PCR-based diagnostic test methods that will enable quick and specific identification of the virus in future disease investigations.
The utilization of solar technology for clean energy generation has seen a dramatic increase over the past decade. Eyeing the ever-growing solar capacity and the subsequent inevitable deluge of solar ...panel wastes, the ideal approach to handle End-of-Life (EoL) solar photovoltaic (PV) panels is to recycle their materials for reuse. This present study explores an optimal recycling process with a high resource recovery efficiency on a laboratory scale, which comprises of three main steps: module delamination, acid etching and sequential electrodeposition. High recoveries of 86, 95 and 97% were achieved for silver, lead and aluminum, respectively. The acquired results are further applied in a life cycle assessment. The process was scaled up to simulate an industrial process and its human and environmental impacts were compared to those of the landfilling disposal method, with six main impact categories analyzed and described: global warming potential, human toxicity potential, freshwater ecotoxicity potential, acidification potential, eutrophication potential and ozone depletion potential. Mitigation strategies are also proposed. Lastly, economic analysis demonstrated that at a treatment capacity of 892.5 kg/h, the process is feasible with an internal revenue rate of 28.2% and a payback time of less than a year, provided the waste collection is subsidized.
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•A large majority of end-of-life PV panels are disposed to landfill.•A recycling process with delamination, etching and eletrodeposition is demonstrated.•The process achieved 86, 95 and 97% recoveries for Ag, Pb and Al respectively.•The GHG emission of recycling is five times lower than that of landfilling.•Process simulation and economic analysis prove the viability of recycling.
Post-translational S-palmitoylation directs the trafficking and membrane localization of hundreds of cellular proteins, often involving a coordinated palmitoylation cycle that requires both protein ...acyl transferases (PATs) and acyl protein thioesterases (APTs) to actively redistribute S-palmitoylated proteins toward different cellular membrane compartments. This process is necessary for the trafficking and oncogenic signaling of S-palmitoylated Ras isoforms, and potentially many peripheral membrane proteins. The depalmitoylating enzymes APT1 and APT2 are separately conserved in all vertebrates, suggesting unique functional roles for each enzyme. The recent discovery of the APT isoform-selective inhibitors ML348 and ML349 has opened new possibilities to probe the function of each enzyme, yet it remains unclear how each inhibitor achieves orthogonal inhibition. Herein, we report the high-resolution structure of human APT2 in complex with ML349 (1.64 Å), as well as the complementary structure of human APT1 bound to ML348 (1.55 Å). Although the overall peptide backbone structures are nearly identical, each inhibitor adopts a distinct conformation within each active site. In APT1, the trifluoromethyl group of ML348 is positioned above the catalytic triad, but in APT2, the sulfonyl group of ML349 forms hydrogen bonds with active site resident waters to indirectly engage the catalytic triad and oxyanion hole. Reciprocal mutagenesis and activity profiling revealed several differing residues surrounding the active site that serve as critical gatekeepers for isoform accessibility and dynamics. Structural and biochemical analysis suggests the inhibitors occupy a putative acyl-binding region, establishing the mechanism for isoform-specific inhibition, hydrolysis of acyl substrates, and structural orthogonality important for future probe development.
The Saccharomyces cerevisiae Fun30 chromatin remodeler has recently been shown to facilitate long-range resection of DNA double strand break (DSB) ends, which proceeds homologous recombination (HR). ...This is believed to underlie the role of Fun30 in promoting cellular resistance to DSB inducing agent camptothecin. We show here that Fun30 also contributes to cellular resistance to genotoxins methyl methanesulfonate (MMS) and hydroxyurea (HU) that can stall the progression of DNA replication. We present evidence implicating DNA end resection in Fun30-dependent MMS-resistance. On the other hand, we show that Fun30 deletion suppresses the MMS- and HU-sensitivity of cells lacking the Rad5/Mms2/Ubc13-dependent error-free DNA damage tolerance mechanism. This suppression is not the result of a reduction in DNA end resection, and is dependent on the key HR component Rad51. We further show that Fun30 negatively regulates the recovery of rad5Δ mutant from MMS induced G2/M arrest. Therefore, Fun30 has two functions in DNA damage repair: one is the promotion of cellular resistance to genotoxic stress by aiding in DNA end resection, and the other is the negative regulation of a Rad51-dependent, DNA end resection-independent mechanism for countering replicative stress. The latter becomes manifest when Rad5 dependent DNA damage tolerance is impaired. In addition, we find that the putative ubiquitin-binding CUE domain of Fun30 serves to restrict the ability of Fun30 to hinder MMS- and HU-tolerance in the absence of Rad5.
Augmented intelligence (AuI) integrates human intelligence (HI) and artificial intelligence (AI) to harness their strengths and mitigate their weaknesses. The combination of HI and AI has seen to ...improve both human and machine capabilities, and achieve a better performance compared to separate HI and AI approaches. In this paper, we present a survey of literature to understand how AuI has been applied in the literature, including the roles of HI and AI, AI approaches, features, and applications. Due to the limited literature related to this topic, we also present a survey of expert opinion to answer four main questions to understand the experts' implications of AuI, including: a) the definition of AuI and the significance of HI in AuI; b) the roles of HI in AuI; c) the current and future applications of AuI in research, industry, and public, as well as the advantages and shortcomings of AuI; and d) end users' view of the application of AuI. We also present recommendations to improve AuI, and provide a comparison between the findings from the surveys of both literature and expert opinion. The discussion of this paper shows the promising potential of AuI compared to separate HI and AI approaches.
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