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Abstract The accumulation of misfolded and aggregated proteins is a hallmark of neurodegenerative proteinopathies. Although multiple genetic loci have been associated with specific neurodegenerative diseases (NDs), molecular mechanisms that may have a broader relevance for most or all proteinopathies remain poorly resolved. In this study, we developed a multi‐layered network expansion (MLnet) model to predict protein modifiers that are common to a group of diseases and, therefore, may have broader pathophysiological relevance for that group. When applied to the four NDs Alzheimer's disease (AD), Huntington's disease, and spinocerebellar ataxia types 1 and 3, we predicted multiple members of the insulin pathway, including PDK1, Akt1, InR, and sgg (GSK‐3β), as common modifiers. We validated these modifiers with the help of four Drosophila ND models. Further evaluation of Akt1 in human cell‐based ND models revealed that activation of Akt1 signaling by the small molecule SC79 increased cell viability in all models. Moreover, treatment of AD model mice with SC79 enhanced their long‐term memory and ameliorated dysregulated anxiety levels, which are commonly affected in AD patients. These findings validate MLnet as a valuable tool to uncover molecular pathways and proteins involved in the pathophysiology of entire disease groups and identify potential therapeutic targets that have relevance across disease boundaries. MLnet can be used for any group of diseases and is available as a web tool at http://ssbio.cau.ac.kr/software/mlnet.

Purpose: The aim of this study was to elucidate the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may initiate cytokine cascades and correlate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with their serum cytokine profiles. Methods: Recombinant baculoviruses displaying SARS-CoV-2 spike or nucleocapsid protein were constructed and transfected into A549 cells and THP-1-derived macrophages, to determine which protein initiate cytokine release. SARS-CoV-2-specific antibody titers and cytokine profiles of patients with COVID-19 were determined, and the results were associated with their clinical characteristics, such as development of pneumonia or length of hospital stay. Results: The SARS-CoV-2 nucleocapsid protein, rather than the spike protein, triggers lung epithelial A549 cells to express IP-10, RANTES, IL-16, MIP-1α, basic FGF, eotaxin, IL-15, PDGF-BB, TRAIL, VEGF-A, and IL-5. Additionally, serum CTACK, basic FGF, GRO-α, IL-1α, IL-1RA, IL-2Rα, IL-9, IL-15, IL-16, IL-18, IP-10, M-CSF, MIF, MIG, RANTES, SCGF-β, SDF-1α, TNF-α, TNF-β, VEGF, PDGF-BB, TRAIL, β-NGF, eotaxin, GM-CSF, IFN-α2, INF-γ, and MCP-1 levels were considerably increased in patients with COVID-19. Among them, patients with pneumonia had higher serum IP-10 and M-CSF levels than patients without. Patients requiring less than 3 weeks to show negative COVID-19 tests after contracting COVID-19 had higher serum IP-10 levels than the remaining patients. Conclusion: Our study revealed that nucleocapsid protein, lung epithelial cells, and IP-10 may be potential targets for the development of new strategies to prevent, or control, severe COVID-19. [ABSTRACT FROM AUTHOR]

Background: Cryopreserved fat has limited clinical applications due to its rapid absorption, high degree of fibrosis, and risk of complications after grafting. Many studies have verified that Adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos) can improve fresh fat graft survival. This study assessed whether ADSC-Exos could improve the survival of cryopreserved fat grafts. Methods: Exosomes were isolated from human ADSCs were subcutaneously engrafted with adipose tissues stored under different conditions (fresh; cryopreserved for 1 month) into the backs of BALB/c nude mice (n = 24), and exosomes or PBS were administered weekly. Grafts were harvested at 1, 2, 4, and 8 weeks, and fat retention rate, histologic, and immunohistochemical analyses were conducted. Results: At 1, 2, and 4 weeks after the transfer, cryopreserved fat grafts in groups of exosome-treated showed better fat integrity, fewer oil cysts, and reduced fibrosis. Further investigations of macrophage infiltration and neovascularization revealed that those exosomes increased the number of M2 macrophages at 2 and 4 weeks (p<0.05), but had limited impact on vascularization (p>0.05). It's important to note that no significant differences (p>0.05) were observed between the two groups in both histological and immunohistochemical evaluations at 8 weeks post-transplantation. Conclusions: This study suggests that ADSC-Exos could improve the survival of cryopreserved fat grafts in the short term (within 4 weeks), but the overall improvement was poor (after 8 weeks). This suggests that the utility of using ADSC-Exos to treat cryopreserved adipose tissue grafts is limited. No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Randomized research demonstrated that robotic surgery was oncologically safe and beneficial in the short term. We investigated whether older adults benefit from robotics more than younger adults do in terms of short-term outcomes. We identified all older (≥ 70 years old) and younger (≤ 70) adults with rectal cancer treated with resection between 2019 and 2022 from an institutional database. We assessed the short-term post-operative 90-day outcomes, which included the first bowel movement, length of hospital duration, sepsis, and harvested lymph node on an age-based differentiation. The key outcomes were complications and grades III–IV on the Clavien–Dindo scale. We identified 298 individuals treated with oncologic resection of rectal cancer: 108 (36.6%) were older adults, while 190 (63.4%) were younger adults. Older adults treated with robotic surgery include 45 (41.6%), whereas 63 (58.3%) older adults were treated with laparoscopic surgery, and 85 (44.7%) younger adults were treated with robotic surgery, while 105 (55.2%) younger adults were treated with laparoscopic surgery. The Clavien–Dindo grading system exposes a substantial P < 0.05 in younger group, whereas grade III–IV patients are seen more frequently in laparoscopic surgery than robotic surgery. Younger and older persons both benefited differently from robotic surgery when compared to laparoscopic surgery in terms of major post-operative complications. [ABSTRACT FROM AUTHOR]

In this paper, we are devoted to the study of a problem proposed in Aujol and Dossal (SIAM J Optim 29:3131–3153, 2019), which concerns the optimal convergence rates for damped inertial gradient dynamics with flat geometries. Fortunately, we find a solution to the problem. More specifically, we obtain an optimal decay rate for the system energy of the second-order differential equation with time-dependent damping in a Hilbert space H x ¨ (t) + γ (t) x ˙ (t) + ∇ F (x (t)) = 0 , where F : H → R is a differentiable convex function possessing at least one minimizer and γ (t) = α / t with α > 0. It is known that this system, with the time-dependent damping coefficient γ (t) , models a nonlinear oscillator with viscous damping, and is associated with the Nesterov acceleration scheme, FISTA, or the accelerated gradient method in the area of numerical optimization. [ABSTRACT FROM AUTHOR]

In this study, ternary and quaternary micro-alloyed copper (MAC) wires were formed by adding trace amounts of gold, palladium, and platinum to copper wires and introducing copper substrates to eliminate the influence of intermetallic compounds on the bonding surface. The reliability of the copper wires and copper substrates after wire bonding were investigated. The results show that the addition of platinum had no grain refinement effect, and the resistance was significantly increased compared to the addition of gold and palladium. However, the platinum-added MAC wire exhibited the best electrical fatigue life whether as a pure wire or bonding with the substrate. After bonding of the MAC wires with the copper substrates, they still retained certain mechanical properties and showed extremely good electrical fatigue characteristics. Overall, the Cu321 wire, with the addition of 0.3 wt.% platinum, 0.2 wt.% gold, and 0.1 wt.% palladium, bonding with copper substrate exhibited the best reliability and can be applied in packaging industries. [ABSTRACT FROM AUTHOR]

This study aimed to assess whether an enzyme-treated pumpkin (Cucurbita moschata Duch.) pulp (EPP) could be applied as an ingredient in bread making. The results showed that EPP treated by pectinase, cellulase, and α-amylase had increased content in reducing sugar but decreased contents in pectin, cellulose, and starch. When EPP was added into wheat flour to replace the added water by 25% or 50% (on fresh basis), the generated dough samples after yeast fermentation showed reduced dough volume but enhanced textural indices including hardness, springiness, and adhesiveness than the control dough. The EPP-supplemented bread samples showed close weight and similar composition in moisture, lipid, protein, and reducing sugar to the control bread, but had higher ash and crude fiber contents. Compared with the control bread, the EPP-supplemented bread samples also showed less baking loss, higher values in four textural indices including hardness, chewiness, springiness, and adhesiveness, lower bread volume and specific volume, and were more red and yellow. Image analysis results confirmed that EPP caused higher cell density but lower cell area and porosity in the bread samples. Interestingly, the untreated pumpkin pulp (PP) was more potent than EPP to affect these assessed indices in both dough and bread samples, while a higher PP/EPP level caused more index changes. Although EPP induced several adverse impacts on both dough and bread quality, it could be regarded a potential ingredient in bread making, because its application at lower level could enhance dietary fiber content and only had less influence on bread quality. [ABSTRACT FROM AUTHOR]

The present study used Chrysomya megacephala larvae (CML) to transform food waste into safe and high-quality fish feed to substitute fish meal as a source of protein for growing Oujiang color common carps followed by a human health risk assessment of polycyclic aromatic hydrocarbons (PAHs). The results showed the ∑PAH concentration in the CML fed with food waste ranged from 50 to 370 μg kg−1, and the most abundant PAH compound in the CML was BaP, contributing 59–84% of ∑PAHs. The Pearson correlation analysis results indicated no correlation between the ∑PAH concentrations and the culture substrate ratio (p > 0.05). Concentrations of BaP in the CML decreased with the increase of breeding density (p < 0.01). The residues as organic fertilizers have no potential ecological risk for PAHs. The biotransformed larva meal was used to partially or completely replace the fish meal as supplementary protein in the experimental feeds (T0, 0%; T50, 50%; T100, 100%). No significant difference (p < 0.05) of survival rate, lipid, and protein content in Oujiang color common carp was noted among T0, T50, and T100 fish feeds. Concentrations of ∑PAHs in Oujiang color common carp fed with the CML fish feeds all met the food safety standards in the European Union (EU). Furthermore, the consumption of Oujiang color common carps fed with the CML feed does not pose any health risks of PAHs for humans. [ABSTRACT FROM AUTHOR]

In this study, trace quantities of silver, palladium, and gold were added to 5 N pure copper wires to prepare microalloyed copper (MAC) wires. The mechanical properties and electrical fatigue mechanisms of original wires and wire bonding specimens were compared to assess the differences between MAC and Au/Pd-coated copper (CPA) wires. The results indicate that the solid-solution strengthening achieved by the addition of trace alloy elements improved the microhardness and tensile properties of the wires; thus, the overall mechanical properties of the MAC wires were superior to those of a CPA wire. Moreover, after wire bonding, the MAC wires exhibited a higher first bond strength than the CPA wire. In terms of electrical properties, the addition of trace alloying elements increased resistance marginally, which resulted in MAC wires with higher dynamic resistance than the CPA wire in the early stage of electrification. At high currents, CPA wires are affected by Joule heat. The palladium atoms in the coating layer diffuse into the wire matrix, which causes the resistance to increase rapidly and thus results in a decreased fusing current. In a power cycling test, the coefficients of thermal expansion of the coating layers were different from that of the wire; thus, the CPA wire was susceptible to thermal fatigue, which led to its failure. The MAC wires had a higher power cycle life than the CPA wire. Because of their superior mechanical and electrical properties, MAC wires can replace CPA wires in the electronic packaging industry. [ABSTRACT FROM AUTHOR]

This is the first investigation that identified seasonal variation, possible sources and health risk of 16 PAHs in street dust sampled park area (PA), educational area (EA), commercial area (CA), residential area (RA), and traffic area (TA) of Chengdu, one of the new first-tier cities in China. The total PAHs (∑16PAHs) concentrations of averaging over two seasons varied from 2.15 to 10.6 mg/kg with a median value of 4.61 mg/kg and in winter (5.48 ± 1.52 mg/kg) were significantly higher than that in summer (4.04 ± 0.91 mg/kg). The highest ∑16PAHs concentration was found in TA (median 6.74 mg/kg). Statistical analysis results indicated that mixture sources of petroleum combustion and combustion of biomass and coal seem to be the primary source of the PAHs in street dust. Carcinogenic risk by incremental lifetime cancer risk (ILCR) model for PAHs in street dust indicates an acceptable potential cancer risk for residents. The same sequences of cancer risk to be observed for both children and adults among different functional areas: TA > CA > EA > RA > PA. The results provided advice for habitants in Chengdu to encourage outdoor activities in parks and residential areas and minimize traffic areas and commercial areas. [ABSTRACT FROM AUTHOR]

Polyphenolic substances kaempferol and quercetin are major flavonols found in plant foods, while caseins are major protein fractions in milk. In this study, the non-covalent interactions involved in the formation of caseinate–flavonol complexes as well as the resultant scavenging activities to three free radicals were assessed by multi-spectroscopic, molecular docking, and chemical assays. The results revealed that the binding of kaempferol/quercetin to caseinate was through a mode of energy transfer, resulting in fluorescence quenching of caseinate; meanwhile, both hydrophobic interaction and H-bonds were the forces involved in the resultant non-covalent caseinate–flavonol interactions. The results from UV-absorption and three-dimensional fluorescence spectra indicated that the two flavonols induced conformational change of caseinate. Moreover, quercetin with two hydroxyl groups at the carbon-4ʹ and -5ʹ positions of the B-ring exerted higher affinity to caseinate than kaempferol with one hydroxyl group at the carbon 4ʹ-position of the B-ring. In addition, the caseinate–quercetin complexes had higher scavenging activities against the DPPH, ABTS, and hydroxyl radicals than the caseinate–kaempferol complexes. In conclusion, both chemical structures and especially hydroxyl group numbers of flavonols are critical to the non-covalent casein–flavonol interactions and radical scavenging activities of the resultant complexes. [ABSTRACT FROM AUTHOR]

This study examined the cognitive-linguistic and literacy-related correlates of dyslexia in three Chinese cities and the English word reading and mathematics performances of Chinese children with dyslexia. Chinese children with/without dyslexia were measured with an equivalent test battery of literacy and mathematics in Beijing, Hong Kong, and Taipei. Univariate analysis results suggested that phonological sensitivity distinguished those with and without dyslexia across all three cities in group comparisons. In Taipei and Hong Kong, morphological awareness, delayed copying, and spelling also distinguished the groups. Logistic regression analyses demonstrated that Chinese character reading, as directly compared to Chinese word reading, also distinguished the groups particularly well. In addition, in Beijing and Hong Kong, children with dyslexia performed significantly less well in English word reading than those without dyslexia. In Hong Kong and Taipei, children with dyslexia also had difficulties in mathematics performance. Findings highlight the fundamental importance of some cognitive-linguistic skills for explaining Chinese dyslexia across cultures, the utility of recognizing the individual Chinese character as a foundational unit of analysis in Chinese across cultures, and the generalizability of the comorbidity of both English as a second language (L2) and mathematics with dyslexia in Chinese children in both Beijing and Hong Kong. [ABSTRACT FROM AUTHOR]