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Purpose. We hypothesize that growth hormone (GH) plays a significant role in the regulation of the meibomian gland. To test our hypothesis, we examined the influence of GH on mouse meibomian gland structure. Methods. We studied four groups of mice, including (1) bovine (b) GH transgenic mice with excess GH; (2) GH receptor (R) antagonist (A) transgenic mice with decreased GH; (3) GHR knockout (-/-) mice with no GH activity; and (4) wild type (WT) control mice. After mouse sacrifice, eyelids were processed for morphological and image analyses. Results. Our results show striking structural changes in the GH-deficient animals. Many of the GHR-/- and GHA meibomian glands featured hyperkeratinized and thickened ducts, acini inserting into duct walls, and poorly differentiated acini. In contrast, the morphology of WT and bGH meibomian glands appeared similar. The sizes of meibomian glands of bGH mice were significantly larger and those of GHA and GHR-/- mice were significantly smaller than glands of WT mice. Conclusions. Our findings support our hypothesis that the GH/IGF-1 axis plays a significant role in the control of the meibomian gland. In addition, our data show that GH modulates the morphology and size of this tissue.
The size modulation of hollow carbon nanospheres (HCSs) has attracted great interest in the contexts of cellular uptake, drug delivery and bioimaging. In this study, a facile fabrication method was specifically used to minimize all influencing factors except for the particle size. A series of nanoparticles of hollow carbon nanospheres embedded with magnetic resonance imaging (MRI) nanoagent γ-Fe2O3 and GdPO4 nanoparticles (Fe-Gd/HCS), were successfully prepared and applied to in vitro/vivo evaluation with well-defined sizes of ∼100 nm (Fe-Gd/HCS-S), ∼200 nm (Fe-Gd/HCS-M), and ∼300 nm (Fe-Gd/HCS-L), respectively. Then the in vitro size effect of Fe-Gd/HCS was systematically investigated by bio-TEM, CLSM, CCK-8 assay, and flow cytometry revealing that Fe-Gd/HCS could be internalized and the cellular uptake amounts increase with the decrease of size. Furthermore, the in vivo size-effect behavior of Fe-Gd/HCS (∼100 nm, ∼200 nm, ∼300 nm) was tracked by MRI technique, demonstrating that all Fe-Gd/HCS can distinguish the liver, in which Fe-Gd/HCS with the smallest particle size exhibited the best performance among these nanoparticles. By leveraging on these features, Fe-Gd/HCS-S (∼100 nm) was further chosen as a theranostic agent, preliminarily presenting its capability for multi-modal imaging and therapy.
Immunosuppressive drugs have shown great promise in treating autoimmune diseases in recent years. A series of novel oxazole derivatives were screened for their immunosuppressive activity. PO-322 [1H-indole-2,3-dione 3-(1,3-benzoxazol-2-ylhydrazone)] was identified as the most effective of these compounds. Here, we have investigated the mechanism(s) underlying the inhibition of T-cell proliferation in vitro by PO-322, as well as its effects on the delayed-type hypersensitivity (DTH) response and imiquimod-induced dermatitis in vivo.
Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA.
The SaCoVLM is a new type of video intubating laryngeal mask airway (LMA), and it is the first LMA to realise continuous visual monitoring. There is a lack of studies on intubation using the SaCoVLM. The aim of this study is to compare the success rate of intubation with polyvinyl chloride (PVC) tubes and wire-reinforced (WR) tubes using the SaCoVLM.
Analysis of a large number of samples requires an efficient, rapid and reproducible method. Automation is an ideal approach for high-throughput sample preparation. Multi-plexing sample preparation via a 96-well plate format becomes popular in recent years; however, those methods lack specificity and require several cleanup steps via chromatography purification. To overcome these drawbacks, a chemoenzymatic method has been developed utilizing protein conjugation on solid-phase. Previously, sample preparation was successfully performed in a snap-cap spin-column (SCSC) format. However, sample preparation using SCSC is time-consuming and lacks reproducibility. In this work, we integrated the chemoenzymatic technique in a pipette tip (AutoTip) that was operated by an automated liquid handler. We established a multi-step protocol involving protein immobilization, sialic acid modification, and N-glycan release. We first optimized our automated protocol using bovine fetuin as a standard glycoprotein, and then assessed the reproducibility of the AutoTip using isobaric tags for relative N-linked glycan quantification. We then applied this methodology to profile N-glycans from 58 prostate cancer patient urine samples, revealing increased sialyation on urinary N-glycans derived from prostate cancer patients. Our results indicated AutoTip has applications for high-throughput sample preparation for studying the N-linked glycans.
Bariatric surgery may be indicated in patients with nonalcoholic fatty liver disease (NAFLD) to achieve and maintain the degree of weight loss required to ensure therapeutic effects. However, bariatric surgery is still underrecognized in the treatment of NAFLD, including its inflammatory subtype, nonalcoholic steatohepatitis (NASH). Moreover, there is a lack of follow-up outcome data on different types of bariatric surgery in patients with NAFLD. This study aims to adequately assess the effect of bariatric surgery on NAFLD remission in obese patients.
Transforaminal lumbar interbody fusion (TLIF) has been widely used in the treatment of lumbar degenerative disc disorders and shows favourable clinical results. Recently, cortical bone trajectory (CBT) has become a new trajectory for screw insertion in the lumbar spine. Several biomechanical studies have demonstrated that the CBT technique achieves screw purchase and strength greater than the traditional method. Currently, the available data on the clinical effectiveness of the two performed surgeries, TLIF with CBT screws (CBT-TLIF) and TLIF with traditional pedicle screws (PS-TLIF), are insufficient. This is the first randomised study to compare CBT-TLIF against traditional PS fixation and will provide recommendations for treating patients with lumbar degenerative disc disorders.
Next generation sequencing (NGS) has been widely used in biological research, due to its rapid decrease in cost and increasing ability to generate data. However, while the sequence generation step has seen many improvements over time, the library preparation step has not, resulting in low-efficiency library preparation methods, especially for the most time-consuming and labor-intensive steps: size-selection and quantification. Consequently, there can be bottlenecks in projects with large sample cohorts.
Neoadjuvant chemotherapy with docetaxel, oxaliplatin, and capecitabine (DOX regimen) is rarely used in Eastern countries and its efficacy and safety in advanced gastric cancer have not been reported. In this open-label, randomized, controlled trial, the authors aimed to assess the clinical efficacy of neoadjuvant chemotherapy using the DOX and oxaliplatin plus capecitabine (XELOX) regimens, in comparison to surgery alone.
Numerous studies have demonstrated an overlap between the processing of self-pain and others' pain, which suggests that psychological and neural representations are shared between the perception of physical pain and empathy for pain. As hearing emotional exclamations is a common way in which we regularly perceive and empathize with others' pain, the present study aimed to investigate the link between sensitivity to physical pain and the sounds made by others in pain. We recorded event-related potential (ERP) responses to another person's vocalizations (neutral or painful intonation) and identified electrophysiological responses associated with the processing of painful sounds. Additionally, individual pain sensitivity was characterized by a stimulus-response function that described the relationship between objective stimulus intensity and subjective pain intensity. Results showed that compared with hearing others' neutral sounds, hearing others' sounds of pain elicited more positive frontal-central N1 and N2 responses as well as more positive central-parietal P3 and late positive potential responses. These electrophysiological responses to hearing others' pain replicated electrophysiological responses to observing pictures and video clips of people in pain. Importantly, the neural responses to hearing others in pain were associated with physical pain sensitivity that was indexed by stimulus-response characteristics. The identified link between perception of one's own physical pain and the sounds of others in pain further supports the shared common psychological computations between processing one's own pain and empathizing with others' pain.
Cryogenic electron microscopy (cryo-EM) is widely used to determine near-atomic resolution structures of biological macromolecules. Due to the low signal-to-noise ratio, cryo-EM relies on averaging many images. However, a crucial question in the field of cryo-EM remains unanswered: how close can we get to the minimum number of particles required to reach a specific resolution in practice? The absence of an answer to this question has impeded progress in understanding sample behavior and the performance of sample preparation methods. To address this issue, we develop an iterative particle sorting and/or sieving method called CryoSieve. Extensive experiments demonstrate that CryoSieve outperforms other cryo-EM particle sorting algorithms, revealing that most particles are unnecessary in final stacks. The minority of particles remaining in the final stacks yield superior high-resolution amplitude in reconstructed density maps. For some datasets, the size of the finest subset approaches the theoretical limit.
Many non-union animal models have been developed to explore the problems surrounding fracture healing. However, the existing models are not perfect and cannot satisfy all non-union studies. This study aimed to make a non-union model of the tibia in rats by cauterization of the posterior of 2 mm on both sides of the fracture end after open osteotomy of the tibia and fixing the fractured tibia with a Kirschner wire 0.8 mm in diameter.
Genetic diversity is one of the key evolutionary variables that correlate with population size, being of critical importance for population viability and the persistence of species. Genetic diversity can also have important ecological consequences within populations, and in turn, ecological factors may drive patterns of genetic diversity. However, the relationship between the genetic diversity of a population and how this interacts with ecological processes has so far only been investigated in a few studies. Here, we investigate the link between ecological factors, local population size, and allelic diversity, using a field study of a common bird species, the house sparrow (Passer domesticus). We studied sparrows outside the breeding season in a confined small valley dominated by dispersed farms and small-scale agriculture in southern France. Population surveys at 36 locations revealed that sparrows were more abundant in locations with high food availability. We then captured and genotyped 891 house sparrows at 10 microsatellite loci from a subset of these locations (N = 12). Population genetic analyses revealed weak genetic structure, where each locality represented a distinct substructure within the study area. We found that food availability was the main factor among others tested to influence the genetic structure between locations. These results suggest that ecological factors can have strong impacts on both population size per se and intrapopulation genetic variation even at a small scale. On a more general level, our data indicate that a patchy environment and low dispersal rate can result in fine-scale patterns of genetic diversity. Given the importance of genetic diversity for population viability, combining ecological and genetic data can help to identify factors limiting population size and determine the conservation potential of populations.
The stratified distribution of bacterial and archaeal communities has been detected in many sediment profiles from various natural environments. A better understanding of microbial composition and diversity pattern in coastal mangrove wetlands in relation to physicochemical and spatial-temporal influences could provide more insights into the ecological functions of microbes in coastal wetlands. In this study, seasonal variations of microbial communities within sediment profiles from two sediment types (mangrove forest and intertidal mudflats) at three sampling locations in coastal Mai Po wetland were characterized using MiSeq high throughput sequencing and 16S rRNA quantitative PCR methods. Bacterial 16S rRNA gene abundance showed clear decreasing trends with increasing depth for all sites, seasonality and sediment types. There is a weak seasonal dynamic of bacterial and archaeal community abundance in both seasons. Seasonality imposed more influence on the beta diversity pattern of bacterial community than archaeal community. The five most abundant phyla within bacterial and archaeal community remain stable between two distinctive seasons. Sediment depth and seasonality are the most influential factors affecting bacterial community composition and diversity. The pH is the most influential factor on shaping the archaeal community. Stratified distribution of bacterial community including aerobic and anaerobic bacterial taxa is largely represented in the surface layers and the subsurface layers, respectively. For archaeal stratification, Thaumarchaeota Marine Group I is the dominant member in surface sediments while Bathyarchaeota and MBG-B dominate in subsurface sediments. Such stratified distribution patterns are irrespective of sediment types, sampling locations or seasonality, but significantly correlated to the sediment depth, which might be shaped by oxygen availability and the distribution of other terminal electron accepters along the depth profile.
Type 2 diabetes mellitus (T2DM) alters brain function and manifests as brain atrophy. Intranasal insulin has emerged as a promising intervention for treatment of cognitive impairment. We evaluated the acute effects of intranasal insulin on resting-state brain functional connectivity in older adults with T2DM. This proof-of-concept, randomized, double-blind, placebo-controlled study evaluated the effects of a single 40 IU dose of insulin or saline in 14 diabetic and 14 control subjects. Resting-state functional connectivity between the hippocampal region and default mode network (DMN) was quantified using functional MRI (fMRI) at 3Tesla. Following insulin administration, diabetic patients demonstrated increased resting-state connectivity between the hippocampal regions and the medial frontal cortex (MFC) as compared with placebo (cluster size: right, P = 0.03) and other DMN regions. On placebo, the diabetes group had lower connectivity between the hippocampal region and the MFC as compared with control subjects (cluster size: right, P = 0.02), but on insulin, MFC connectivity was similar to control subjects. Resting-state connectivity correlated with cognitive performance. A single dose of intranasal insulin increases resting-state functional connectivity between the hippocampal regions and multiple DMN regions in older adults with T2DM. Intranasal insulin administration may modify functional connectivity among brain regions regulating memory and complex cognitive behaviors.
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