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TDP-43 inclusions are found in many Alzheimer's disease (AD) patients presenting faster disease progression and greater brain atrophy. Previously, we showed full-length TDP-43 forms spherical oligomers and perturbs amyloid-β (Aβ) fibrillization. To elucidate the role of TDP-43 in AD, here, we examined the effect of TDP-43 in Aβ aggregation and the attributed toxicity in mouse models. We found TDP-43 inhibited Aβ fibrillization at initial and oligomeric stages. Aβ fibrillization was delayed specifically in the presence of N-terminal domain containing TDP-43 variants, while C-terminal TDP-43 was not essential for Aβ interaction. TDP-43 significantly enhanced Aβ's ability to impair long-term potentiation and, upon intrahippocampal injection, caused spatial memory deficit. Following injection to AD transgenic mice, TDP-43 induced inflammation, interacted with Aβ, and exacerbated AD-like pathology. TDP-43 oligomers mostly colocalized with intracellular Aβ in the brain of AD patients. We conclude that TDP-43 inhibits Aβ fibrillization through its interaction with Aβ and exacerbates AD pathology.

Highlights Bulk molding compound (BMC) manufactured using fiber reinforced polymers (FRPs) has attracted extensive attention and is widely used because of its capability to fabricate structures with complex shapes. This study investigated the effects of aging on the mechanical properties of BMC composites made using an epoxy matrix and discontinuous carbon fibers of varying lengths. Tensile, compressive, and flexural tests were conducted. The results showed that longer fibers did not necessarily increase the moduli and strengths of BMC composites due to stress concentrations resulting from the curling and entanglement of the longer fibers. When aged, BMC composites using shorter carbon fibers exhibited more significant reductions in moduli and strengths due to higher void contents, resulting in more severe matrix epoxy degradation. When comparing epoxy and BMC, BMC experienced greater reductions in moduli and strengths even though carbon fiber, a type of artificial fiber, should be less affected by aging. This is because aging not only degraded the matrix epoxy but also affected the adhesion between the fibers and the matrix, leading to a larger displacement of the fibers, resulting in a more severe reduction in the mechanical properties of the BMC composites. BMC composites were manufactured using epoxy and discontinuous carbon fibers. Longer fibers did not necessarily increase strengths due to entanglement. BMC using shorter fibers had more voids and hence degraded more severely. BMC showed greater strength reductions than epoxy due to matrix degradation. Degradation of matrix epoxy affected the adhesion between fibers and matrix. [ABSTRACT FROM AUTHOR]

Composite sandwich structures are widely used in many areas. Light materials, such as honeycomb panels, are usually used as the cores, while stiff materials, such as fiber reinforced polymer laminates, are used as the facesheets. In this work, corrugated cores for sandwich structures were fabricated using carbon fiber reinforced polymers (CFRPs) featuring different stacking orientations. Paper, aluminum, and polypropylene honeycomb cores were also used. Additionally, CFRP was utilized as the facesheets for these sandwich structures. Bending tests, face-wise compression tests (FCT), edgewise compression tests (ECT), and accelerated aging were conducted. Finite element simulations were also performed and compared with experimental results. The results indicated that the corrugated CFRP cores with [0°]5 stacking orientation resulted in the largest flexural stiffness and ECT strength along the flute direction. Conversely, the corrugated cores with [90°]5 stacking orientation resulted in the largest transverse shear rigidity and modulus, FCT modulus and strength, and ECT strength perpendicular to the flute direction. Notably, the sandwich structures using aluminum honeycomb cores were degraded by aging the least. Since sandwich structures can be subjected to the bending load and loads in other directions, this work contributes to selecting core materials and structures of sandwich structures. [ABSTRACT FROM AUTHOR]

This paper proposes a broadband eight-antenna array design suitable for Fifth Generation New Radio (5G NR) smartphone applications. To cover the 5G NR bands n77/n78/n79 (3300–5000 MHz) and 5G NR-U n46 band (5150–5925 MHz), the single antenna array unit applied is a modified loop antenna element (MLAE) that can generate three different loop modes. To yield good multi-input multi-output (MIMO) performances, the designed MLAE is further arranged as an eight-antenna array, and the experimental results show that the overlapping 6 dB bandwidth can cover the bands-of-interest (3300–5925 MHz) with good isolation and total efficiency of >10 dB and 51–84%, respectively. Finally, good MIMO performances, such as an envelope correlation coefficient (ECC) of lower than 0.1 and desirable channel capacity (CC) of 37–40 bps/Hz, were calculated across the bands-of-interest. [ABSTRACT FROM AUTHOR]

The long noncoding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and pathophysiological functions in the cell. We identified from RNA-Seq profiling a set of lncRNAs in cultured human umbilical vein endothelial cells (HUVECs) that are differentially regulated by atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated lncRNAs, including both known and novel transcripts, LINC00341 is one of the most abundant lncRNAs in endothelial cells. Moreover, its expression level is enhanced by atheroprotective pulsatile shear flow and atorvastatin. Overexpression of LINC00341 suppresses the expression of vascular cell adhesion molecule 1 (VCAM1) and the adhesion of monocytes induced by atheroprone flow and tumor necrosis factor-alpha. Underlying this anti-inflammatory role, LINC00341 guides enhancer of zest homolog 2, a core histone methyltransferase of polycomb repressive complex 2, to the promoter region of the VCAM1 gene to suppress VCAM1. Network analysis reveals that the key signaling pathways (e.g., Rho and PI3K/AKT) are co-regulated with LINC00341 in endothelial cells in response to pulsatile shear. Together, these findings suggest that LINC00341, as an example of lncRNAs, plays important roles in modulating endothelial function in health and disease.

Purpose: To compare the biomechanical properties of the slip‐knot technique with three other transtibial pullout suture repair constructs for meniscal root tears. Method: Thirty‐two fresh‐frozen cadaveric menisci were randomly allocated to four meniscus‐suture fixation constructs: Two simple‐sutures (TSS), two slip‐knot (TSK) sutures, two cinch‐loop (TCL) sutures, and two modified Mason–Allen (TMMA) sutures. Cyclic loading from 5 to 20 N was conducted for 1000 cycles at 0.5 Hz, and then loaded to failure at 0.5 mm/s. Parametric data (displacement during cyclic loading, ultimate load, yield load, and displacement at failure) were analysed using a one‐way analysis of variance (ANOVA), whereas nonparametric data (stiffness) were analysed using the Kruskal–Wallis test. Results: After 1000 cycles, the TCL construct significantly displaced the most (mean ± SD, 6.78 ± 1.32 mm; p < 0.001), followed by the TMMA (2.83 ± 0.90 mm), TSK (2.33 ± 0.57 mm), and TSS (2.03 ± 0.62 mm) groups. On ultimate failure load, there was no significant difference between the TSK group (123.48 ± 27.24 N, p > 0.05) and the other three groups (TSS, 94.65 ± 25.33 N; TMMA, 168.38 ± 23.24 N; TCL, 170.54 ± 57.32 N); however, it exhibited the least displacement (5.53 ± 1.25 mm) which was significantly shorter than those of the TCL (11.82 ± 4.25 mm, p < 0.001) and TMMA (9.53 ± 2.18 mm, p = 0.03) constructs. No significant difference in stiffness was observed among the four meniscus‐suture constructs. Conclusion: The slip‐knot technique has proven to be a simple, yet robust and stable meniscal root fixation option; moreover, it exhibited superiority over the more complex modified Mason–Allen suture construct in resisting displacement at the ultimate failure load. Level of Evidence: Not applicable. [ABSTRACT FROM AUTHOR]

Combining microbial products with different mechanisms of action can produce synergistic insecticidal effects and slow down the development of resistance. This study evaluated the insecticidal activity of mixtures containing the commercial Photorhabdus luminescens (Pl) strain ATCC 29,999, the local isolate Pl 2103-UV, and the commercial Bacillus thuringiensis subsp. kurstaki (Bt) ABTS-351 against Spodoptera frugiperda. As the proportion of Bt increased in the mixtures, insecticidal activity increased, with the synergistic ratios reaching 1.98 for ATCC 29,999 and 5.29 for 2103-UV at a1:5 Pl:Bt ratio, representing approximately twofold and fivefold reductions, respectively, in the Bt dosage required for mortality. Hemolymph analysis revealed the highest Pl bacterial loads in the 1:5 treatments within the S. frugiperda hemocoel. Histopathology also showed exacerbated midgut vacuolation in the 1:5 ATCC 29,999:Bt treatment. Whole-genome analysis showed that 2103-UV produced more porins, potentially contributing to its higher insecticidal activity. This study demonstrated that Bt assists the invasion of Pl into the hemocoel and enhances synergistic insecticidal efficiency. The findings provide a reference for integrating Pl with other microbial products to sustainably manage significant and severe lepidopteran pests. [ABSTRACT FROM AUTHOR]

The Developmental Origins of Health and Disease (DOHaD) concept has gained prominence in maternal and child health (MCH), emphasizing how early-life factors impact later-life non-communicable diseases. However, a knowledge–practice gap exists in applying DOHaD principles among healthcare professionals. Healthy Early Life Moments in Singapore (HELMS) introduced webinars to bridge this gap and empower healthcare professionals. We aimed to conduct a preliminary assessment to gain early insights into the outreach and effectiveness of the educational initiative offered with the HELMS webinars. We employed a pragmatic serial cross-sectional study approach and targeted healthcare professionals involved in MCH care. We also collected and analyzed data on webinar registration and attendance, participants' profession and organizational affiliations, and post-webinar survey responses. The median webinar attendance rate was 59.6 % (25th–75th percentile: 58.4–60.8 %). Nurses represented 68.6 % of attendees (n=2,589 out of 3,774). Post-webinar surveys revealed over 75 % of the participants providing positive responses to 14 out of 15 survey questions concerning content, delivery, applicability to work, and organization. Assessment of the HELMS webinars provided insight into the outreach and early effectiveness in enhancing healthcare professionals' knowledge and confidence in delivering DOHaD education. Bridging the knowledge–practice gap remains a crucial goal. [ABSTRACT FROM AUTHOR]