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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.

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]

Abstract Background SUMOylation, as part of the epigenetic regulation of transcription, has been intensively studied in lower eukaryotes that contain only a single SUMO protein; however, the functions of SUMOylation during mammalian epigenetic transcriptional regulation are largely uncharacterized. Mammals express three major SUMO paralogues: SUMO-1, SUMO-2, and SUMO-3 (normally referred to as SUMO-1 and SUMO-2/3). Herpesviruses, including Kaposi’s sarcoma associated herpesvirus (KSHV), seem to have evolved mechanisms that directly or indirectly modulate the SUMO machinery in order to evade host immune surveillance, thus advancing their survival. Interestingly, KSHV encodes a SUMO E3 ligase, K-bZIP, with specificity toward SUMO-2/3 and is an excellent model for investigating the global functional differences between SUMO paralogues. Results We investigated the effect of experimental herpesvirus reactivation in a KSHV infected B lymphoma cell line on genomic SUMO-1 and SUMO-2/3 binding profiles together with the potential role of chromatin SUMOylation in transcription regulation. This was carried out via high-throughput sequencing analysis. Interestingly, chromatin immunoprecipitation sequencing (ChIP-seq) experiments showed that KSHV reactivation is accompanied by a significant increase in SUMO-2/3 modification around promoter regions, but SUMO-1 enrichment was absent. Expression profiling revealed that the SUMO-2/3 targeted genes are primarily highly transcribed genes that show no expression changes during viral reactivation. Gene ontology analysis further showed that these genes are involved in cellular immune responses and cytokine signaling. High-throughput annotation of SUMO occupancy of transcription factor binding sites (TFBS) pinpointed the presence of three master regulators of immune responses, IRF-1, IRF-2, and IRF-7, as potential SUMO-2/3 targeted transcriptional factors after KSHV reactivation. Conclusion Our study is the first to identify differential genome-wide SUMO modifications between SUMO paralogues during herpesvirus reactivation. Our findings indicate that SUMO-2/3 modification near protein-coding gene promoters occurs in order to maintain host immune-related gene unaltered during viral reactivation.

The impact of vitamin D supplementation on 25-hydroxyvitamin D (25OHD) levels, metabolic status, and pregnancy outcomes in pregnant women with overweight and obesity (OW/OB) is uncertain. This study aimed to examine whether administrating 800 IU of vitamin D3 orally would improve maternal serum 25OHD levels, lipid profile, and pregnancy outcomes compared to 400 IU. This was a two-arm, parallel, non-blinded randomised controlled trial involving 274 pregnant women recruited from KK Women's and Children's Hospital, with a body mass index of ≥25 kg/m2 within 16 weeks gestation. The participants were randomly assigned to receive 800 IU/day (intervention group) or 400 IU/day (control group) of oral vitamin D3 supplements. The primary outcomes were maternal serum 25OHD and lipid levels at 24–28 weeks gestation. The secondary outcomes included maternal and birth outcomes. Compared with controls (n = 119), the intervention group (n = 112) exhibited higher 25OHD levels at 24–28 weeks gestation (adjusted mean difference 6.52 nmol/L; 95% confidence interval 2.74, 10.31). More women in the intervention group achieved sufficient 25OHD levels (77.7% vs. 55.5%; p < 0.001). No differences were observed in lipid profiles or maternal or birth outcomes between the groups. An additional 400 IU of oral vitamin D3 supplementation increased serum 25OHD levels but did not impact lipid profiles or pregnancy outcomes. [ABSTRACT FROM AUTHOR]

In this study, we comprehensively investigate the constant voltage stress (CVS) time-dependent breakdown and cycle-to-breakdown while considering metal-ferroelectric-metal (MFM) memory, which has distinct domain sizes induced by different doping species, i.e., Yttrium (Y) (Sample A) and Silicon (Si) (Sample B). Firstly, Y-doped and Si-doped HfO2 MFM devices exhibit domain sizes of 5.64 nm and 12.47 nm, respectively. Secondly, Si-doped HfO2 MFM devices (Sample B) have better CVS time-dependent breakdown and cycle-to-breakdown stability than Y-doped HfO2 MFM devices (Sample A). Therefore, a larger domain size showing higher extrapolated voltage under CVS time-dependent breakdown and cycle-to-breakdown evaluations was observed, indicating that the domain size crucially impacts the stability of MFM memory. [ABSTRACT FROM AUTHOR]

Developing sensitive diagnostic methods for a longitudinal evaluation of the status of liver fibrosis is a priority. This study is aimed at assessing the significance of longitudinal positron emission tomography (PET) imaging with 18F-labeling tracers for assessing liver fibrosis in a rat model with bile duct ligation (BDL). Twenty-one 6-week-old Sprague-Dawley male rats were used in this study. Longitudinal PET images using [18F]N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA) (n = 3), [18F]fluoroacetate ([18F]FAc) (n = 3), and 18F-fluoro-2-deoxy-D-glucose ([18F]FDG) (n = 3) were obtained at 0, 1, and 2 weeks after BDL. Biochemical assays, histological assays, immunohistochemical staining assays, and next generation sequencing analyses were also performed at 0 (n = 3), 1 (n = 3), 2 (n = 3), and 3 (n = 3) weeks after BDL, which demonstrated the severe damage in rat livers after BDL. Regarding [18F]FEPPA and [18F]FDG, there was a significantly higher uptake in the liver after BDL (both P < 0.05), which lasted until week 2. However, the uptake of [18F]FAc in the liver was not significantly different before and after BDL (P = 0.28). Collectively, both [18F]FEPPA and [18F]FDG can serve as sensitive probes for detecting the liver fibrosis. However, [18F]FAc is not recommended to diagnose liver fibrosis. [ABSTRACT FROM AUTHOR]