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Approaches to regenerating bone often rely on integrating biomaterials and biological signals in the form of cells or cytokines. However, from a translational point of view, these approaches are challenging due to the sourcing and quality of the biologic, unpredictable immune responses, complex regulatory paths, and high costs. We describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system (CSS) that offers distinct advantages for clinical translation. The CSS comprises a 3D-printed porous polydiolcitrate-hydroxyapatite composite elastomer infused with a polydiolcitrate-graphene oxide hydrogel composite. Using a micro-continuous liquid interface production 3D printer, we fabricate a precise porous ceramic scaffold with 60 wt% hydroxyapatite resembling natural bone. The resulting scaffold integrates with a thermoresponsive hydrogel composite in situto fit the defect, which is expected to enhance surface contact with surrounding tissue and facilitate biointegration. The antioxidative properties of citrate polymers prevent long-term inflammatory responses. The CSS stimulates osteogenesis in vitroand in vivo. Within 4 weeks in a calvarial critical-sized bone defect model, the CSS accelerated ECM deposition (8-fold) and mineralized osteoid (69-fold) compared to the untreated. Through spatial transcriptomics, we demonstrated the comprehensive biological processes of CSS for prompt osseointegration. Our material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages, potentially expediting clinical application for bone reconstruction surgeries.

This numerical study examined the effects of a curved turning vane on the heat transfer and pressure loss of a four-pass internal cooling channel. Three-dimensional omega-based Reynolds stress (RSM-ω) turbulence model equations were used in the computation process. Three different curved turning vane configurations were studied using a simple, without a turning vane under stationary and rotating conditions for Reynolds numbers between 20,000 and 60,000 and a rotation number of 0.042. The numerical results showed good agreement with previous experimental data. Under both stationary and rotating conditions, the curved turning vane in a hub turn reduced the pressure drop significantly compared to the conventional turning vanes. Although a curved turning vane attenuated overall heat transfer, the local heat transfer increased it in particular regions, such as the hub turn and the fourth turn of cooling passages, particularly in cases with smaller radii. Coolant flow through the hub turn of the serpentine channel can reduce recirculation, separation, and flow impingement, which are unfavorable factors of pressure loss, owing to the semi-circular configuration of the curved turning vane. Regarding the rotating conditions, four-pass channels with a smaller radius of a curved turning vane provide better overall cooling performance.

Autophagy, an intracellular recycling system, is essential for the meiotic maturation of porcine oocytes. Trehalose has been reported as a novel mammalian target of rapamycin (mTOR)-independent autophagy inducer in many cells. Furthermore, we previously have demonstrated that trehalose supplementation during in vitro maturation of porcine oocytes improves the developmental competence of parthenogenetic embryos, possibly via autophagic activation, whereas the underlying mechanisms remain unclear. Therefore, the aim of this study was to address this issue. We found that trehalose plays a role as an autophagy activator by autophagic flux assay and determined that it promotes phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) inhibition and vacuolar protein sorting 34 (VPS34)/mTOR activation by immunoblotting, both in cumulus cells (CCs) and oocytes. However, interestingly, the effects and the mechanisms regulated by trehalose were different in them, respectively. In CCs, the autophagy was activated through the improvement of lysosomal function/autophagic clearance viability by upregulation of coordinated lysosomal expression and regulation genes via PI3K/Akt inhibition. Whereas in oocytes, autophagy was activated via induction of VPS34, which directly influences autophagosome formation, and the precise meiotic process was ensured via Akt inhibition and mTOR activation. Taken together, this study furtherly elucidates the novel detailed mechanism of trehalose during porcine oocyte maturation, thus laying the biological foundations for pharmacological application.

Background: Genetically modified pigs are considered ideal models for studying human diseases and potential sources for xenotransplantation research. However, the somatic cell nuclear transfer (SCNT) technique utilized to generate these cloned pig models has low efficiency, and fetal development is limited due to placental abnormalities. Results: In this study, we unprecedentedly established putative porcine trophoblast stem cells (TSCs) using SCNT and in vitro-fertilized (IVF) blastocysts through the activation of Wing-less/Integrated (Wnt) and epidermal growth factor (EGF) pathways, inhibition of transforming growth factor-β (TGFβ) and Rho-associated protein kinase (ROCK) pathways, and supplementation with ascorbic acid. We also compared the transcripts of putative TSCs originating from SCNT and IVF embryos and their differentiated lineages. A total of 19 porcine TSCs exhibiting typical characteristics were established from SCNT and IVF blastocysts (TSCsNTand TSCsIVF). Compared with the TSCsIVF, TSCsNTshowed distinct expression patterns suggesting unique TSCsNTcharacteristics, including decreased mRNA expression of genes related to apposition, steroid hormone biosynthesis, angiopoiesis, and RNA stability. Conclusion: This study provides valuable information and a powerful model for studying the abnormal development and dysfunction of trophoblasts and placentas in cloned pigs.

Polyaspartamide, derived from polysuccinimide (PSI), has the advantage of conveniently presenting desired functional groups by ring-opening addition of amine-based nucleophiles to the succinimidyl ring moieties of PSI. Using diamines with varying lengths of poly(ethylene glycol) linker, polyaspartamide presenting amine groups with controllable grafting density and length, namely, poly(2-hydroxyethyl aspartamide)-g-amino-poly(ethylene glycol) (PHEA–PEGAm) could be synthesized. This PHEA–PEGAm was then used to develop in situ forming hydrogels by Schiff base formation with aldehyde-containing alginate (Alg-ALD). By modulating the graft architecture (i.e., grafting length and density), the mechanical properties of the resulting Alg-PHEA hydrogels could be controlled in a broad range. Remarkably, the hydrogels were shown to undergo facile degradation and complete dissolution in physiological conditions, regardless of hydrogel mechanics, by the expedited hydrolysis through the action of remaining amine groups, which was also heavily influenced by the graft architecture. Moreover, the rate of degradation could be further controlled by additional ionic cross-linking of alginate. The potential application as an injectable drug delivery system was demonstrated by measuring drug release kinetics and monitoring degradation ex vivo.

Here, we present a three-dimensional two-color dual-particle tracking (3D-2C-DPT) technique that can simultaneously localize two spectrally distinct targets in three dimensions with a time resolution down to 5 ms. The dual-targets can be tracked with separation distances from 33 to 250 nm with tracking precisions of ∼15 nm (for static targets) and ∼35 nm (for freely diffusing targets). Since each target is individually localized, a wealth of data can be extracted, such as the relative 3D position, the 2D rotation, and the separation distance between the two targets. Using this technique, we turn a double-stranded DNA (dsDNA)-linked dumbbell-like dimer into a nanoscopic optical ruler to quantify the bending dynamics of nicked or gapped dsDNA molecules in free solution by manipulating the design of dsDNA linkers (1-nick, 3-nt, 6-nt, or 9-nt single-strand gap), and the results show the increase of kon(linear to bent) from 3.2 to 10.7 s–1. The 3D-2C-DPT is then applied to observe translational and rotational motions of the landing of an antibody-conjugated nanoparticle on the plasma membrane of living cells, revealing the reduction of rotations possibly due to interactions with membrane receptors. This study demonstrates that this 3D-2C-DPT technique is a new tool to shed light on the conformational changes of biomolecules and the intermolecular interactions on plasma membrane.

Purpose: Many empirical studies have focused on whether public funding leverages (crowds in) or discourages (crowds out) private giving behavior, finding mixed results. Recent studies suggest the need to examine how nonprofits adjust their fundraising efforts after experiencing cuts or increases in government funding, which can then influence donor behavior. Design/methodology/approach: In this study, the authors conduct an online survey experiment with nonprofit managers to test how nonprofits respond to changes in government funding. Findings: The authors find some evidence that nonprofit organizations would change their fundraising expenses when facing cuts in government funding, yet the authors also find that the change could be either to increase or decrease fundraising spending. Since decisions are made by executive directors, the study also considered how executive personality type as maximizers or satisficers may interact with institutional and environmental constraints in decision-making. When funding goals are met, executives tend to behave as “satisficers” and are unlikely to make significant changes, even when their individual personality is more consistent with being a “maximizer.” Research limitations/implications: The authors find these results to be the reflection of the current environment in which many nonprofits operate, characterized by pressures to keep operating costs low. The results of the experiment have implications for both funding agencies and nonprofits that strive to enhance the capacity of nonprofit services. Originality/value: This study is the first attempt to untangle the multilayered relationships between government funding, fundraising, leader preferences and personalities, and donations using an experimental approach with current nonprofit leaders.

This paper examined the performance of a conical hydrodynamic bearing with MR lubricant by three-dimensional CFD simulations using finite element analysis. The main innovative aspect of this research is the development of a realistic model for controllable MR conical bearing at low shear rates and a magnetic field. Points such as the prediction of the plug formation zones and their detailed analysis of conical bearing considering the yield stress as a function of the magnetic field are among the key issues that were addressed in analyzing these fluids. The study’s significant focus is predicting and analyzing the plug formation zones in the conical bearing, which are difficult to detect at low shear rates. The Maxwell and Cauchy momentum equations are solved, and the Bingham–Papanastasiou constitutive equation is used to describe the properties of the MR fluid. The results of this study were validated based on the former analytical, numerical, and experimental data. The bearing's performance is evaluated based on several parameters, including eccentricity, conical angle, aspect ratio, and various yield stress types. The results indicate that despite the challenges and difficulties of using MRFs, they can enhance the bearing's performance and increase its load capacity.

Charities in the United States are allowed to engage in lobbying activities, but many choose not to. Charitable nonprofits, such as hospitals, social service providers, museums, and environmental organizations, can directly contact lawmakers or engage in grassroots lobbying to influence legislation. The Internal Revenue Service (IRS) assesses charities' lobbying activities and sets limits on how much time and money they can spend on lobbying based on their size. Charities must report their lobbying activities when filing their tax forms, except for churches and congregations, which have to follow a "substantial part" test. While charities can engage in educational efforts on issues of public policy, they cannot endorse political candidates or make donations to lawmakers. Nonprofit lobbying is regulated by both federal and state laws, and failure to comply with these regulations can result in fines or loss of tax-exempt status. [Extracted from the article]

A moment magnitude 5.4 earthquake struck the Pohang city located in the southeastern Korean Peninsula on 15 November 2017, possibly triggered by an enhanced geothermal system. Despite the moderate magnitude of the earthquake, extensive geotechnical and structural damage occurred. This study summarizes the widespread geotechnical damage resulted from the Pohang earthquake, observed during our reconnaissance trip. The affected area is mainly covered by Tertiary/Quaternary Alluvium underlain by mudstones with a thickness of approximately 500 m. Because of the soft grounds and shallow focal depth, this area experienced ground settlements up to 39 cm, building settlements that made apartments tilted by 1.6°. We also present observations on ground cracks, lateral spreadings, landslides, retaining wall deformations, and liquefactions. Documenting the damage is significant because (1) those are the first earthquake-induced damage observed in Korea, and (2) those are caused by the shallow-depth earthquake possibly induced by an enhanced geothermal system.

Growth differentiation factor 8 (GDF8), also known as myostatin, is a member of the transforming growth factor-β (TGF-β) family and has been identified as a strong physiological regulator of muscle differentiation. Recently, the functional role of GDF8 in reproductive organs has received increased interest following its detection in the human placenta and uterus. To investigate the effects of GDF8 during porcine oocyte in vitro maturation (IVM), we assessed the quality of matured oocytes. Furthermore, we investigated the specific gene transcription and protein activation levels in oocytes and cumulus cells after IVM and subsequent embryonic development after in vitro fertilization and parthenogenetic activation. Prior to these experiments, the concentration of GDF8 in porcine follicular fluid was determined. During the entire IVM period, 1.3 ng/mL GDF8 and its signaling inhibitor SB431542 (SB) at 5 μM were added as control, SB, SB + GDF8, and GDF8 groups, respectively. Our results demonstrate that supplementation with GDF8 during porcine oocyte IVM enhanced both meiotic and cytoplasmic maturation, with altered transcriptional patterns, via activation of Sma- and Mad-related protein 2/3 (SMAD2/3). Using the pharmacological inhibitor SB431542, we demonstrated that inhibition of GDF8-induced Smad2/3 signaling reduces matured oocyte quality. In conclusion, for the first time, we demonstrated paracrine factor GDF8 in porcine follicular fluid in vivo. Furthermore, we showed that GDF8 supplementation improved mature oocyte quality by regulating p38 mitogen-activated protein kinase phosphorylation and intracellular glutathione and reactive oxygen species levels during porcine IVM.

The advent of 3D printing has had a disruptive impact in manufacturing and can potentially revolutionize industrial fields. Thermoplastic materials printable into complex structures are widely employed for 3D printing. Polylactic acid (PLA) is among the most promising polymers used for 3D printing, owing to its low cost, biodegradability, and nontoxicity. However, PLA is electrically insulating and mechanically weak; this limits its use in a variety of 3D printing applications. This study demonstrates a straightforward and environment-friendly method to fabricate conductive and mechanically reinforced PLA composites by incorporating graphene nanoplatelets (GNPs). To fully utilize the superior electrical and mechanical properties of graphene, liquid-exfoliated GNPs are dispersed in isopropyl alcohol without the addition of any surfactant and combined with PLA dissolved in chloroform. The GNP–PLA composites exhibit improved mechanical properties (improvement in tensile strength by 44% and maximum strain by 57%) even at a low GNP threshold concentration of 2 wt %. The GNP–PLA composites also exhibit an electrical conductivity of over 1 mS/cm at >1.2 wt %. The GNP–PLA composites can be 3D-printed into various features with electrical conductivity and mechanical flexibility. This work presents a new direction toward advanced 3D printing technology by providing higher flexibility in designing multifunctional 3D printed features.

Ammonia is a promising fuel as not only a carbon-free fuel, but also as a hydrogen carrier. Blending ammonia with hydrogen is an effective method to tackle ammonia's low flammability problem. However, there is a lack of data regarding ammonia combustion at the microscale. In the present study, two-dimensional numerical simulations were performed to investigate ammonia/hydrogen's stable flame region, NOx emission, and combustion efficiency in micro-combustors. For these purposes, the effects of inlet flow velocity and the hydrogen fraction of the fuel on the combustion characteristics and temperature distribution were analyzed. It has been found that a stable flame cannot exist when the inlet velocity is too low relative to the flame speed or too high in accordance with the heating of the wall. Furthermore, a stable flame does not appear when the hydrogen fraction is less than 60% in the fuel. In terms of emission, increasing the inlet flow velocity increases NO emission at every hydrogen fraction of the fuel, and the maximum NO produced increases by approximately 120% when the inlet flow velocity changes from 50 to 200 cm/s. Reduction of the inlet flow velocity is suggested when a higher percentage of ammonia is required in the fuel to recover the loss of combustion efficiency.

Supplemental Digital Content is Available in the Text.A thinner lamina cribrosa was observed in both eyes of unilateral branch retinal occlusion (BRVO) patients compared with that of healthy subjects. A thin lamina as a local mechanical factor, in addition to possible systemic factors, may be involved in the pathogenesis of BRVO and may partially explain the high coincidence of glaucoma in these patients.

•Identification of Ammonia combustion regime map in a counterflow configuration.•Various combustion regimes were achieved by increasing the temperature of the oxidizer and dilution level for different thermal Energy entering the system.•The stability and Emission characteristics are studied from a combustion regime viewpoint.•Species and NO sensitivity analysis have been done to observe the effect of the regime transition on the reactions and Species.

•Supersonic ejector system was experimentally applied at low-temperature conditions.•A numerical method was used to optimize the ejector.•ER was enhanced up to 33.66% by the optimization process compared to the baseline.•The modified geometry experimentally and numerically showed ER of about 1.06.

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