A Metabolomics Study on the Bone Protective Effects of a Lignan-Rich Fraction From Sambucus Williamsii Ramulus in Aged Rats

The lignan-rich fraction (SWR) of Sambucus Williamsii Ramulus, a folk herbal medicine in China for treatment of bone diseases, has previously reported to exert protective effects on bone without exerting uterotrophic effects in ovariectomized (OVX) mice. The aim of the present study was to identify the potential metabolites and the associated metabolic pathways that contribute to the beneficial effects of SWR on bone in vivo. Aged female Sprague Dawley rats (9 months old) were either sham-operated or ovariectomized for 12 weeks, before receiving treatment for another 12 weeks with the following treatment groups (n = 12 each): vehicle (Sham), vehicle (OVX), Premarin (130 μg/kg) or low (57 mg/kg), medium (114 mg/kg), and high (228 mg/kg) doses of SWR. The results showed that SWRH significantly suppressed bone loss, improved bone micro-architecture and increased bone strength on tibia without stimulating uterus weight gain in OVX rats. Premarin exerted similar bone protective effects as SWRH but elicited uterotrophic effects in OVX rats. The metabolic profiles of serum samples were analyzed by using ultra-performance liquid chromatography quadrupole time-of flight mass spectrometry and gas chromatography time-of flight mass spectrometry, and the metabolites that were significantly altered were identified by multivariate statistical analysis. Our study indicated that SWRH effectively restored the changes of 26 metabolites induced by estrogen-deficiency in OVX rats, which related to lipids, amino acids, tryptophan metabolisms, and anti-oxidative system. A subsequent validation showed that the serum level of superoxide dismutase and catalase were indeed up-regulated, while the serotonin level in a tryptophan hydroxylase 1 (TPH1) high expressing cells (rats RBL-2H3 cells) was down regulated after treatment with SWR. The results also suggested that the gut-microbiota may play an important role on the bone protective effects of SWR. The current study provides insight for understanding the unique mechanism of actions of SWR that might be involved in achieving bone protective effects in vivo

Basic Amino Acid Mutations in the Nuclear Localization Signal of Hibiscus Chlorotic Ringspot Virus p23 Inhibit Virus Long Distance Movement

10.1371/journal.pone.0074000PLoS ONE89-POLN

Biophysical and nutritional combination treatment for myosteatosis in patients with sarcopenia: a study protocol for single-blinded randomised controlled trial

Introduction Sarcopenia is characterised by age-related loss of skeletal muscle and function and is associated with risks of adverse outcomes. The prevalence of sarcopenia increases due to ageing population and effective interventions is in need. Previous studies showed that β-hydroxy β-methylbutyrate (HMB) supplement and vibration treatment (VT) enhanced muscle quality, while the coapplication of the two interventions had further improved muscle mass and function in sarcopenic mice model. This study aims to investigate the efficacy of this combination treatment in combating sarcopenia in older people. The findings of this study will demonstrate the effect of combination treatment as an alternative for managing sarcopenia. Methods and analysis In this single-blinded randomised controlled trial, subjects will be screened based on the Asian Working Group for Sarcopenia (AWGS) 2019 definition. 200 subjects who are aged 65 or above and identified sarcopenic according to the AWGS algorithm will be recruited. They will be randomised to one of the following four groups: (1) Control+ONS; (2) HMB+ONS; (3) VT+ONS and (4) HMB+VT + ONS, where ONS stands for oral nutritional supplement. ONS will be taken in the form of protein formular once/day; HMB supplements will be 3 g/day; VT (35 Hz, 0.3 g, where g=gravitational acceleration) will be received for 20 mins/day and at least 3 days/week. The primary outcome assessments are muscle strength and function. Subjects will be assessed at baseline, 3-month and 6-month post treatment. Ethics and dissemination This study was approved by Joint CUHK-NTEC (The Chinese University of Hong Kong and New Territories East Cluster) Clinical Research Management Office (Ref: CRE-2022.223-T) and conformed to the Declaration of Helsinki. Trial results will be published in peer-reviewed journals and disseminated at academic conferences

Exonic remnants of whole-genome duplication reveal cis-regulatory function of coding exons

Using a comparative genomics approach to reconstruct the fate of genomic regulatory blocks (GRBs) and identify exonic remnants that have survived the disappearance of their host genes after whole-genome duplication (WGD) in teleosts, we discover a set of 38 candidate cis-regulatory coding exons (RCEs) with predicted target genes. These elements demonstrate evolutionary separation of overlapping protein-coding and regulatory information after WGD in teleosts. We present evidence that the corresponding mammalian exons are still under both coding and non-coding selection pressure, are more conserved than other protein coding exons in the host gene and several control sets, and share key characteristics with highly conserved non-coding elements in the same regions. Their dual function is corroborated by existing experimental data. Additionally, we show examples of human exon remnants stemming from the vertebrate 2R WGD. Our findings suggest that long-range cis-regulatory inputs for developmental genes are not limited to non-coding regions, but can also overlap the coding sequence of unrelated genes. Thus, exonic regulatory elements in GRBs might be functionally equivalent to those in non-coding regions, calling for a re-evaluation of the sequence space in which to look for long-range regulatory elements and experimentally test their activity

Receptor-targeted liposome-peptide-siRNA nanoparticles represent a novel and efficient therapeutic approach to prevent conjunctival fibrosis.

There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye

A 30-Year Worldwide Research Productivity of Scientific Publication in Full-Endoscopic Decompression Spine Surgery: Quantitative and Qualitative Analysis

Objective The ever-growing number of articles related to full-endoscopic spine surgery published in the last few decades presents a challenge which is perplexing and time-consuming in identifying the current research status. The study aims to identify and analyze the most cited works related to full-endoscopic decompression spine surgery, compare the articles published by different publishers and area, and show the current publication status of full-endoscopic research. Methods Using Bibliometrix, CiteSpace, and VOSviewer, we analyzed the bibliometric data selected from the Web of Science database between 1992 and 2022. Spine has the highest H-index with the most-cited journal in the field of full-endoscopic decompression spine surgery. China ranked as the most productive country, whereas the most cited with high H-index papers came from South Korea. For the author analysis, Yeung AT, Ruetten S, Hoogland T, Ahn Y, Choi G, and Mayer HM were the most impactful authors in the global and local citations. The most productive organization is Wooridul Spine Hospital. Conclusion The bibliometric study showed a growing trend of research on full-endoscopic decompression spine surgery over the past 30 years. It has demonstrated that there is a significant increase in the number of authors, institutions, and internationally collaborated countries. However, the quality of studies is still low, and the lack of high-quality clinical evidence and the trend of general journal submissions has somewhat affected the quality of endoscopy journals in recent years

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field