Impacts of Maternal Nutrition on Sow Performance and Potential Positive Effects on Piglet Performance.

The objectives of this review are to identify the nutritional challenges faced by modern sows and present potential solutions to mitigate excessive maternal tissue loss and reproductive failure as it relates to recent genetic improvements. Current feeding programs have limitations to support the rapid genetic improvements in reproductive performance for modern sows. Since 2012, both litter size at birth and fetal weight have increased by 2.26 pigs per litter and 0.22 kg per piglet, respectively, thereby increasing the nutrient needs for sows during gestation and lactation. Prediction models generated in this review predict that modern sows would need 31% more lysine during gestation when compared with current feeding programs. Physiological challenges facing modern sows are also addressed in this review. High oxidative stress, pelvic organ prolapse, and lameness can directly affect the sow, whereas these physiological challenges can have negative impacts on colostrum and milk quality. In response, there is growing interest in investigating the functional roles of select bioactive compounds as feed additives to mitigate the severity of these challenges. Selenium sources, catechins, and select plant extracts have been utilized to reduce oxidative stress, calcium chloride and phytase have been used to mitigate pelvic organ prolapse and lameness, algae and yeast derivatives have been used to improve colostrum and milk quality, and fiber sources and probiotics have been commonly utilized to improve sow intestinal health. Collectively, this review demonstrates the unique challenges associated with managing the feeding programs for modern sows and the opportunities for revision of the amino acid requirements as well as the use of select bioactive compounds to improve reproductive performance.

Comprehensive Overview of Alzheimer's Disease: Etiological Insights and Degradation Strategies.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and affects millions of individuals globally. AD is associated with cognitive decline and memory loss that worsens with aging. A statistical report using U.S. data on AD estimates that approximately 6.9 million individuals suffer from AD, a number projected to surge to 13.8 million by 2060. Thus, there is a critical imperative to pinpoint and address AD and its hallmark tau protein aggregation early to prevent and manage its debilitating effects. Amyloid-ß and tau proteins are primarily associated with the formation of plaques and neurofibril tangles in the brain. Current research efforts focus on degrading amyloid-ß and tau or inhibiting their synthesis, particularly targeting APP processing and tau hyperphosphorylation, aiming to develop effective clinical interventions. However, navigating this intricate landscape requires ongoing studies and clinical trials to develop treatments that truly make a difference. Genome-wide association studies (GWASs) across various cohorts identified 40 loci and over 300 genes associated with AD. Despite this wealth of genetic data, much remains to be understood about the functions of these genes and their role in the disease process, prompting continued investigation. By delving deeper into these genetic associations, novel targets such as kinases, proteases, cytokines, and degradation pathways, offer new directions for drug discovery and therapeutic intervention in AD. This review delves into the intricate biological pathways disrupted in AD and identifies how genetic variations within these pathways could serve as potential targets for drug discovery and treatment strategies. Through a comprehensive understanding of the molecular underpinnings of AD, researchers aim to pave the way for more effective therapies that can alleviate the burden of this devastating disease.

LMT AMI Caused by a Valve-Like Ridge in a 9-Year-Old Boy Successfully Treated With PCI.

A 9-year-old boy was suspected of having acute myocardial infarction and emergency coronary angiogram was performed. No signs of flow limitation in either coronary artery was detected. We performed intravascular ultrasonography from the ascending aorta, which showed a ridge on the left main trunk acting like a valve, resulting in significant stenosis. Percutaneous coronary intervention with stent deployment was performed with good result.

Interleukin Receptor Therapeutics Attenuate Inflammation in Canine Synovium following Cruciate Ligament Injury.

OBJECTIVE: In the knee, synovial fibrosis after ligamentous injury is linked to progressive joint pain and stiffness. The objective of this study was to evaluate changes in synovial architecture, mechanical properties, and transcriptional profiles following naturally occurring cruciate ligament injury in canines and to test potential therapeutics that target drivers of synovial inflammation and fibrosis. DESIGN: Synovia from canines with spontaneous cruciate ligament tears and from healthy knees were assessed via histology (n=10/group) and micromechanical testing (n=5/group) to identify changes in tissue architecture and stiffness. Additional samples (n=5/group) were subjected to RNA-sequencing to define the transcriptional response to injury. Finally, synovial tissue samples from injured animals (n=6 (IL1) or n=8 (IL6)/group) were assessed in vitro for response to therapeutic molecules directed against interleukin (IL) signaling (IL1 or IL6). RESULTS: Cruciate injury resulted in increased synovial fibrosis, vascularity, inflammatory cell infiltration, and intimal hyperplasia. Additionally, the stiffness of both the intima and subintima regions were higher in diseased compared to healthy tissue. Differential gene expression analysis showed that diseased synovium had an upregulation of immune response and cell adhesion pathways and a downregulation of Rho protein transduction pathways. In vitro application of small molecule therapeutics targeting IL1 (anakinra) or IL6 (tocilizumab) dampened expression of inflammatory and matrix deposition mediators. CONCLUSION: Spontaneous cruciate ligament injury in canines is associated with synovial inflammation and fibrosis in a relevant model for testing emerging intra-articular treatments. Small molecule therapeutics targeting IL pathways may be ideal interventions for delivery to the joint space after injury.

Disentangling brain atrophy heterogeneity in Alzheimer's disease: a deep self-supervised approach with interpretable latent space.

Alzheimer's disease (AD) is heterogeneous, but existing methods for capturing this heterogeneity through dimensionality reduction and unsupervised clustering have limitations when it comes to extracting intricate atrophy patterns. In this study, we propose a deep learning based self-supervised framework that characterizes complex atrophy features using latent space representation. It integrates feature engineering, classification, and clustering to synergistically disentangle heterogeneity in Alzheimer's disease. Through this representation learning, we trained a clustered latent space with distinct atrophy patterns and clinical characteristics in AD, and replicated the findings in prodromal Alzheimer's disease. Moreover, we discovered that these clusters are not solely attributed to subtypes but also reflect disease progression in the latent space, representing the core dimensions of heterogeneity, namely progression and subtypes. Furthermore, longitudinal latent space analysis revealed two distinct disease progression pathways: medial temporal and parietotemporal pathways. The proposed approach enables effective latent representations that can be integrated with individual-level cognitive profiles, thereby facilitating a comprehensive understanding of AD heterogeneity.

Meditation-type specific reduction in infra-slow activity of electroencephalogram.

Purpose: Meditation is renowned for its positive effects on cognitive abilities and stress reduction. It has been reported that the amplitude of electroencephalographic (EEG) infra-slow activity (ISA, < 0.1 Hz) is reduced as the stress level decreases. Consequently, we aimed to determine if EEG ISA amplitude decreases as a result of meditation practice across various traditions. Methods: To this end, we analyzed an open dataset comprising EEG data acquired during meditation sessions from experienced practitioners in the Vipassana tradition-which integrates elements of focused attention and open monitoring, akin to mindfulness meditation-and in the Himalayan Yoga and Isha Shoonya traditions, which emphasize focused attention and open monitoring, respectively. Results: A general trend was observed where EEG ISA amplitude tended to decrease in experienced meditators from these traditions compared to novices, particularly significant in the 0.03-0.08 Hz band for Vipassana meditators. Therefore, our analysis focused on this ISA frequency band. Specifically, a notable decrease in EEG ISA amplitude was observed in Vipassana meditators, predominantly in the left-frontal region. This reduction in EEG ISA amplitude was also accompanied by a decrease in phase-amplitude coupling (PAC) between the ISA phase and alpha band (8-12 Hz) amplitude, which implied decreased neural excitability fluctuations. Conclusion: Our findings suggest that not only does EEG ISA amplitude decrease in experienced meditators from traditions that incorporate both focused attention and open monitoring, but this decrease may also signify a diminished influence of neural excitability fluctuations attributed to ISA.

Endohepatology in clinical practice: EUS-guided portal pressure measurement combined with EUS-guided liver biopsy and variceal screening and treatment in outpatients.

Background and Objectives: EUS-guided portal pressure gradient (PPG) is a novel technique that permits a true, direct measure of portal vein pressure and hepatic vein pressure. This article details our experience and lessons learned from 20 consecutive outpatient EUS-PPG procedures performed at a single center, along with simultaneous EUS-guided liver biopsy, variceal screening, and variceal banding. Methods: Data on the first 20 patients who underwent EUS-PPG at a single center were retrospectively viewed and analyzed. The effects of various liver diseases or other patient-related factors on the clinical and technical success of EUS-PPG measurements, as well as EUS-guided liver biopsy (EUS-LB), were evaluated. During the procedure, if esophageal varices were encountered, they were assessed, and if felt to be clinically indicated, endoscopic variceal ligation was performed. Results: The 20 patients included 10 male and 10 female patients. All procedures were technically successful. In all patients, the portal vein and hepatic veins could be easily identified. One adverse event of bleeding occurred during the EUS-PPG measuring procedure. All 20 EUS-LBs were technically successful and yielded adequate samples for histological evaluations, with an average of 25 complete portal tracts per sample. Among patients with esophageal varices, 40% of patients underwent banding. The mean EUS-PPG among 5 patients with esophageal varices was 11.6 mm Hg, compared with 3.2 mm Hg among 15 patients without esophageal varices. Conclusion: This study demonstrates that EUS-PPG is a novel, safe, reproducible, and effective technique. Also, the fact that EUS-PPG, EUS-LB, variceal screening, and variceal banding could be performed in 1 session and on an outpatient basis speaks to the growing relevance and impact of the nascent field of endohepatology.

Catalytic enantioselective [3+2] and [4+2]-annulation of cyclic N-sulfonyl ketimines with γ- or δ-hydroxy-α,ß-unsaturated ketones.

A highly efficient asymmetric [3+2] and [4+2]-annulation of cyclic N-sulfonyl ketimines with γ- or δ-hydroxy-α,ß-unsaturated ketones has been developed. This innovative reaction employs an organocatalytic approach, utilizing a hydrogen-bonding bifunctional squaramide-based catalyst. The process enables precise synthesis of chiral polyheterotricyclic oxazolidines and 1,3-oxazinane derivatives, revealing intricate structures with incorporated chiral quaternary centers. Remarkably, this method delivers high yields and exceptional enantioselectivities and diastereoselectivities, achieving up to 99% yield, >20 : 1 dr, and >99% ee.

Complete genome sequence of Pseudomonas aeruginosa strain NCTR 501 isolated from the inner ear of a laboratory mouse (Mus musculus) diagnosed with otitis media.

We report the circularized 6,427,509-bp genome of Pseudomonas aeruginosa isolated from the inner ear of a laboratory mouse (Mus musculus) diagnosed with otitis media. The genome of P. aeruginosa NCTR 501 has a circular chromosome of 6,420,288 bp and two plasmids of 4,042 and 3,179 bp, respectively.

Solar-Driven Sustainability: III-V Semiconductor for Green Energy Production Technologies.

Long-term societal prosperity depends on addressing the world's energy and environmental problems, and photocatalysis has emerged as a viable remedy. Improving the efficiency of photocatalytic processes is fundamentally achieved by optimizing the effective utilization of solar energy and enhancing the efficient separation of photogenerated charges. It has been demonstrated that the fabrication of III-V semiconductor-based photocatalysts is effective in increasing solar light absorption, long-term stability, large-scale production and promoting charge transfer. This focused review explores on the current developments in III-V semiconductor materials for solar-powered photocatalytic systems. The review explores on various subjects, including the advancement of III-V semiconductors, photocatalytic mechanisms, and their uses in H2 conversion, CO2 reduction, environmental remediation, and photocatalytic oxidation and reduction reactions. In order to design heterostructures, the review delves into basic concepts including solar light absorption and effective charge separation. It also highlights significant advancements in green energy systems for water splitting, emphasizing the significance of establishing eco-friendly systems for CO2 reduction and hydrogen production. The main purpose is to produce hydrogen through sustainable and ecologically friendly energy conversion. The review intends to foster the development of greener and more sustainable energy source by encouraging researchers and developers to focus on practical applications and advancements in solar-powered photocatalysis.

Negative Regulation of CPSF6 Suppresses the Warburg Effect and Angiogenesis Leading to Tumor Progression Via c-Myc Signaling Network: Potential Therapeutic Target for Liver Cancer Therapy.

In this study, we explored the oncogenic mechanism of cleavage and polyadenylation-specific factor 6 (CPSF6) in hepatocellular carcinoma (HCC). CPSF6 was overexpressed in HCC tissues with poor survival rates compared to normal tissues. Hence, CPSF6 depletion suppressed cell viability and colony formation, induced apoptosis via PARP cleavage, and increased the sub-G1 population of Hep3B and Huh7 cells. In addition, CPSF6 enhanced the stability of c-Myc via their binding through nuclear co-localization by binding to c-Myc at the site of 258-360. Furthermore, c-Myc degradation by CPSF6 depletion was disturbed by FBW7 depletion or treatment with the proteasomal inhibitor MG132. Additionally, CPSF6 depletion suppressed the Warburg effect by inhibiting glucose, HK2, PKM2, LDH, and lactate; showed a synergistic effect with Sorafenib in Hep3B cells; and inhibited angiogenesis by tube formation and CAM assays, along with decreased expression and production of vascular endothelial growth factor (VEGF). Notably, CPSF6 depletion attenuated PD-L1 expression and increased Granzyme B levels, along with an increase in the percentage of CD4/CD8 cells in the splenocytes of BALB/c nude mice bearing Hep3B cells. Consistently, immunohistochemistry showed that CPSF6 depletion reduced the growth of Hep3B cells in BALB/c mice in orthotopic and xenograft tumor models by inhibiting tumor microenvironment-associated proteins. Overall, these findings suggest that CPSF6 enhances the Warburg effect for immune escape and angiogenesis, leading to cancer progression via c-Myc, mediated by the HK, PD-L1, and VEGF networks, with synergistic potential with sorafenib as a molecular target for liver cancer therapy.

Conditional spatial biased intuitionistic clustering technique for brain MRI image segmentation.

In clinical research, it is crucial to segment the magnetic resonance (MR) brain image for studying the internal tissues of the brain. To address this challenge in a sustainable manner, a novel approach has been proposed leveraging the power of unsupervised clustering while integrating conditional spatial properties of the image into intuitionistic clustering technique for segmenting MRI images of brain scans. In the proposed technique, an Intuitionistic-based clustering approach incorporates a nuanced understanding of uncertainty inherent in the image data. The measure of uncertainty is achieved through calculation of hesitation degree. The approach introduces a conditional spatial function alongside the intuitionistic membership matrix, enabling the consideration of spatial relationships within the image. Furthermore, by calculating weighted intuitionistic membership matrix, the algorithm gains the ability to adapt its smoothing behavior based on the local context. The main advantages are enhanced robustness with homogenous segments, lower sensitivity to noise, intensity inhomogeneity and accommodation of degree of hesitation or uncertainty that may exist in the real-world datasets. A comparative analysis of synthetic and real datasets of MR brain images proves the efficiency of the suggested approach over different algorithms. The paper investigates how the suggested research methodology performs in medical industry under different circumstances including both qualitative and quantitative parameters such as segmentation accuracy, similarity index, true positive ratio, false positive ratio. The experimental outcomes demonstrate that the suggested algorithm outperforms in retaining image details and achieving segmentation accuracy.

Effects of Acute Beetroot Juice Supplementation and Exercise on Cardiovascular Function in Healthy Men in Preliminary Study: A Randomized, Double-Blinded, Placebo-Controlled, and Crossover Trial.

Nitrate-rich beetroot juice (NRBRJ) can potentially enhance exercise performance and improve cardiovascular function, leading to an increased use of NRBRJ over the years. However, the combined effects of NRBRJ supplementation and exercise on cardiovascular function remain unclear. Therefore, this study compared cardiovascular function responses to submaximal exercise with either placebo (PLA) or NRBRJ supplementation in healthy men. Twelve healthy men (aged 25.2 ± 2.3 years) completed the 30-min submaximal cycle ergometer exercise trials corresponding to 70% maximal heart rate (HRmax) with either PLA or NRBRJ supplementation in a random order. The mean exercise load, heart rate (HR), stroke volume (SV), cardiac output (CO), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and total peripheral resistance (TPR) were measured during exercise. The brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) were measured before and after exercise. NRBRJ supplementation was more effective than PLA in increasing the mean exercise load and decreasing DBP and MAP during submaximal exercise. Furthermore, baPWV decreased in the NRBRJ trial and was considerably lower after exercise in the NRBRJ-supplemented group than in the PLA-supplemented group. FMD significantly increased in the PLA and NRBRJ trials; however, NRBRJ supplementation demonstrated a significantly higher FMD before and after exercise than PLA supplementation. In conclusion, acute NRBRJ supplementation and exercise were more effective than PLA supplementation and exercise in improving aerobic exercise capacity and cardiovascular function in healthy men.

Silkworm (Bombyx mori L.) Has Beneficial Effects on Menopausal Symptoms by Enhancing Estrogen Receptor Signaling in Ovariectomized Mice.

Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.

Investigation of [11C]carfentanil for mu opioid receptor quantification in the rat brain.

[11C]Carfentanil ([11C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [11C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [11C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [11C]CFN PET scans over a wide range of molar activities. Baseline [11C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BPND) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained < 40 ng/kg (~ 10% MOR occupancy in rats), baseline MOR availability was significantly decreased. For test-retest variability (TRTV), better reproducibility was achieved by controlling CFN injected mass to limit the difference between scans. Taken together, we report significant cardiorespiratory depression and a paradoxical influence on baseline MOR availability at conventional tracer doses in rats. Our findings might reflect changes in cerebral blood flow, changes in receptor affinity, or receptor internalization, and merits further mechanistic investigation. In conclusion, rat [11C]CFN PET requires stringent quality assurance of radiotracer synthesis and mass injected to avoid pharmacological effects and limit potential influences on MOR quantification and reproducibility.

Association of changes in predicted body composition with subsequent risk of dementia.

OBJECTIVE: The effect of body composition change on the risk of dementia is not clear. This study analyzed the associations of changes in predicted lean body mass index (pLBMI), predicted appendicular skeletal muscle mass index (pASMI), and predicted body fat mass index (pBFMI) with the risk of dementia. METHODS: In this nationwide cohort study, data were obtained from the Korean National Health Insurance Service database. The exposure was defined as changes in pLBMI, pASMI, and pBFMI derived from validated prediction equations. The outcome was dementia, defined based on the dementia diagnosis with prescription of anti-dementia medication. Cox proportional hazards regression analyses were performed to obtain the hazard ratio with a 95% confidence interval for risk of dementia according to changes in predicted body composition. RESULTS: A total of 13,215,208 individuals with no prior record of dementia who underwent health screenings twice between 2009-2010 and 2011-2012 were included. A 1-kg/m2 increase in pLBMI and pASMI had an association with reduced risk of dementia (aHR: 0.85, 95% CI 0.84-0.87; aHR: 0.70, 95% CI 0.69-0.72, respectively for men, and aHR: 0.69, 95% CI 0.67-0.71; aHR: 0.59, 95% CI 0.57-0.61, respectively for women). A 1-kg/m2 increase in pBFMI had an association with a raised risk of dementia (aHR: 1.19, 95% CI 1.17-1.21 for men and aHR: 1.53, 95% CI 1.48-1.57 for women). These results remained consistent regardless of sex or weight change. INTERPRETATION: Increase in pLBMI or pASMI, or reduction in pBFMI was linked to lower risk of dementia.

The Reconstruction of Pt(001) Surface and the Shell-Like Reconstruction of the Vicinal Pt(001) Surfaces Revealed by Neural Network Potential.

In this work, a highly accurate neural network potential (NNP) is presented, named PtNNP, and the exploration of the reconstruction of the Pt(001) surface and its vicinal surfaces with it. Contrary to the most accepted understanding of the Pt(001) surface reconstruction, the study reveals that the main driving force behind Pt(001) quasi-hexagonal reconstruction is not the surface stress relaxation but the increased coordination number of the surface atoms resulting in stronger intralayer binding in the reconstructed surface layer. In agreement with experimental observations, the optimized supercell size of the reconstructed Pt(001) surface contains (5 × 20) unit cells. Surprisingly, the reconstruction of the vicinal Pt(001) surfaces leads to a smooth shell-like surface layer covering the whole surface and diminishing sharp step edges.

Topological Fermi-arc surface state covered by floating electrons on a two-dimensional electride.

Two-dimensional electrides can acquire topologically non-trivial phases due to intriguing interplay between the cationic atomic layers and anionic electron layers. However, experimental evidence of topological surface states has yet to be verified. Here, via angle-resolved photoemission spectroscopy (ARPES) and scanning tunnelling microscopy (STM), we probe the magnetic Weyl states of the ferromagnetic electride [Gd2C]2+·2e-. In particular, the presence of Weyl cones and Fermi-arc states is demonstrated through photon energy-dependent ARPES measurements, agreeing with theoretical band structure calculations. Notably, the STM measurements reveal that the Fermi-arc states exist underneath a floating quantum electron liquid on the top Gd layer, forming double-stacked surface states in a heterostructure. Our work thus not only unveils the non-trivial topology of the [Gd2C]2+·2e- electride but also realizes a surface heterostructure that can host phenomena distinct from the bulk.

Vestibular hair cells are more prone to damage by excessive acceleration insult in the mouse with KCNQ4 dysfunction.

KCNQ4 is a voltage-gated K+ channel was reported to distribute over the basolateral surface of type 1 vestibular hair cell and/or inner surface of calyx and heminode of the vestibular nerve connected to the type 1 vestibular hair cells of the inner ear. However, the precise localization of KCNQ4 is still controversial and little is known about the vestibular phenotypes caused by KCNQ4 dysfunction or the specific role of KCNQ4 in the vestibular organs. To investigate the role of KCNQ4 in the vestibular organ, 6-g hypergravity stimulation for 24 h, which represents excessive mechanical stimulation of the sensory epithelium, was applied to p.W277S Kcnq4 transgenic mice. KCNQ4 was detected on the inner surface of calyx of the vestibular afferent in transmission electron microscope images with immunogold labelling. Vestibular function decrease was more severe in the Kcnq4p.W277S/p.W277S mice than in the Kcnq4+/+ and Kcnq4+/p.W277S mice after the stimulation. The vestibular function loss was resulted from the loss of type 1 vestibular hair cells, which was possibly caused by increased depolarization duration. Retigabine, a KCNQ activator, prevented hypergravity-induced vestibular dysfunction and hair cell loss. Patients with KCNQ4 mutations also showed abnormal clinical vestibular function tests. These findings suggest that KCNQ4 plays an essential role in calyx and afferent of type 1 vestibular hair cell preserving vestibular function against excessive mechanical stimulation.