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Investigate the predictive value of TyG and lipid ratios on the development of complications and HUA in patients with T2DM. A retrospective cross-sectional study involving 9488 T2DM patients was conducted. They were divided into HUA and NUA group base on SUA level and divided into with and without complications groups according to the diagnosis of the endocrinologist. Necessary information and biochemical parameters were recorded during outpatient visit. TyG index and lipid ratios were calculated, and statistical analysis was carried out to correlate the calculated values and HUA using SPSS version 26.0 for Windows. TyG and lipid ratios were significantly higher in T2DM with HUA or with complications than those with NUA or without complications (p < 0.05). Regression analysis adjusting for confounding factors found TyG (adjusted OR = 1.54; 95% CI: 1.31-1.82; p < 0.05), TG/HDL-C (adjusted OR = 1.21; 95% CI: 1.04-1.40; p < 0.05) and TC/HDL (adjusted OR = 1.36; 95% CI: 1.17-1.57; p < 0.05) was risk factor of HUA in T2DM patients. TyG (adjusted OR = 1.21; 95% CI: 1.02-1.44; p < 0.05), TG/HDL (adjusted OR = 1.19; 95% CI: 1.03-1.38; p < 0.05) and Apo A/Apo B (adjusted OR = 1.41; 95% CI: 1.26-1.58; p < 0.05) was risk factor of complications in T2DM patients. TyG, TG/HDL-C, and TC/HDL can be used as early sensitive target in the occurrence of HUA in T2DM patients and TyG was the most influential risk factor. TyG, TG/HDL-C, and Apo A/Apo B can be used as early sensitive target in the occurrence of complications in T2DM patients and Apo A/Apo B was the most influential risk factor.
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Introduction: The study aimed to investigate the potential effects of varying wheat levels in broiler diets on growth performance, intestinal barrier, and cecal microbiota. Methods: Day-old male broilers were fed the same diet until 10 d of age. Then they were randomly assigned to 1) the low-level wheat group, where inclusion of 15.0% and 25.0% wheat in the grower and finisher diet, respectively, 2) the medium-level wheat group with 30.0% and 40.0% of wheat in the grower and finisher periods; and 3) the high-level wheat dietary group, in which the grower and finisher diets contained 55.77% and 62.38% of wheat, respectively. Results: Dietary treatments unaffected the body weight at 39 d, whereas incorporating high wheat in diets significantly increased the feed intake and reduced the feed conversion ratio from 10 to 39 d (p < 0.05). Except for increased phosphorus digestibility in the high wheat group, dietary treatments had no significant effect on the apparent digestibility of dry matter, crude protein, and ether extract. Meanwhile, the broilers that consumed the medium and high content of wheat presented a higher villus height and the ratio of villus height to crypt depth than those fed the low-level wheat birds. Feeding the medium-level wheat enhanced ileal integrity and depressed the expression of proinflammatory cytokines in the ileum. The addition of high levels of wheat reduced the Chao1 index and the abundance of Lactobacillaceae, Bacteroidaceae, and Ruminococcacea in cecal content, which probably decreased the metabolism of histidine, sulfur-containing amino acids, and the biosynthesis of lysine. Discussion: These results support the medium-level wheat diet improved intestinal barrier function and had no deleterious effects on the growth performance of broiler; dietary inclusion of high wheat reduced the feed conversion rate, which might be associated with the disturbed gut microbiota and decreased metabolism of amino acids.
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Flueggea virosa (Roxb. ex Willd.) Royle, an evergreen shrub and small tree in the Phyllanthaceae family, holds significant potential in garden landscaping and pharmacological applications. However, the lack of genomic data has hindered further scientific understanding of its horticultural and medicinal values. In this study, we have assembled a haplotype-resolved genome of F. virosa for the first time. The two haploid genomes, named haplotype A genome and haplotype B genome, are 487.33 Mb and 477.53 Mb in size, respectively, with contig N50 lengths of 31.45 Mb and 32.81 Mb. More than 99% of the assembled sequences were anchored to 13 pairs of pseudo-chromosomes. Furthermore, 21,587 and 21,533 protein-coding genes were predicted in haplotype A and haplotype B genomes, respectively. The availability of this chromosome-level genome fills the gap in genomic data for F. virosa and provides valuable resources for molecular studies of this species, supporting future research on speciation, functional genomics, and comparative genomics within the Phyllanthaceae family.
Subject(s)
Genome, Plant , Chromosomes, Plant , Haplotypes , Molecular Sequence AnnotationABSTRACT
Dracaena cambodiana Pierre ex Gagn. (Asparagaceae) is the source plant of Dragon's blood and has high ornamental values in gardening. Currently, this species is classified as the second-class state-protected species in the National Key Protected Wild Plants (NKPWP) of China. However, limited genomic data has hindered a more comprehensive scientific understanding of the processes involved in the production of Dragon's blood and the related conservation genomics research. In this study, we assembled a haplotype-resolved genome of D. cambodiana. The haploid genomes, haplotype A and haplotype B, are 1,015.22 Mb and 1,003.13 Mb in size, respectively. The completeness of haplotype A and haplotype B genomes was 98.60% and 98.20%, respectively, using the "embryophyta_10" dataset. Haplotype A and haplotype B genomes contained 27,361 and 27,066 protein-coding genes, respectively, with nearly all being functionally annotated. These findings provide new insights into the genomic characteristics of D. cambodiana and will offer additional genomic resources for studying the biosynthesis mechanism of Dragon's blood and the horticultural application of Dragon trees.
Subject(s)
Dracaena , Genome, Plant , Haplotypes , Dracaena/genetics , China , Chromosomes, Plant/genetics , Plant ExtractsABSTRACT
Background: The efficacy of bioresorbable vascular scaffolds (BVS) compared to metallic stents for the treatment of coronary heart disease remains controversial. The analysis of clinical outcomes at five years following the initial treatment has yet to be reviewed. This study sought to assess the five-year outcomes in randomized controlled trials of BVS in the treatment of coronary heart disease using a systematic review and meta-analysis. Methods: A systematic database search was conducted from their inception to June 30th, 2023 using various Medical Subject Headings (MeSH) terms including: "Coronary Disease", "Bioresorbable stent", "Randomized controlled trials". Results: After a rigorous selection process, a total of five high-quality articles were finally included in this study. Each trial demonstrated a low risk of bias. After 5 years, bioresorbable stents showed outcomes similar to conventional metal stents in terms of cardiac mortality. However, they were inferior in terms of lesion revascularization rates, in-stent thrombosis rates, target lesion failure, target vessel failure, and myocardial infarction. Conclusions: While bioresorbable stents are comparable to metallic stents in terms of cardiac mortality rates, they exhibit significant drawbacks that warrant clinical consideration.
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EcGUS has drawn considerable attention for its role as a target in alleviating serious GIAEs. In this study, a series of 72 (thio)urea derivatives were designed, synthesised, and biologically assayed. The bioassay results revealed that E-9 (IC50 = 2.68 µM) exhibited a promising inhibitory effect on EcGUS, surpassing EcGUS inhibitor D-saccharic acid-1,4-lactone (DSL, IC50 = 45.8 µM). Additionally, the inhibitory kinetic study indicated that E-9 (Ki = 1.64 µM) acted as an uncompetitive inhibitor against EcGUS. The structure-activity relationship revealed that introducing an electron-withdrawing group into the benzene ring at the para-position is beneficial for enhancing inhibitory activity against EcGUS. Furthermore, molecular docking analysis indicated that E-9 has a strong affinity to EcGUS by forming interactions with residues Asp 163, Tyr 472, and Glu 504. Overall, these results suggested that E-9 could be a potent EcGUS inhibitor, providing valuable insights and guidelines for the development of future inhibitors targeting EcGUS.
Subject(s)
Dose-Response Relationship, Drug , Drug Design , Enzyme Inhibitors , Escherichia coli , Glucuronidase , Structure-Activity Relationship , Molecular Structure , Escherichia coli/drug effects , Escherichia coli/enzymology , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Glucuronidase/antagonists & inhibitors , Glucuronidase/metabolism , Molecular Docking Simulation , Thiourea/pharmacology , Thiourea/chemistry , Thiourea/chemical synthesis , GlycoproteinsABSTRACT
BACKGROUND AND OBJECTIVE: Multiple randomized controlled studies have shown that pirfenidone and nintedanib are effective and safe for treating idiopathic pulmonary fibrosis. This study aimed to evaluate their efficacy, safety, and tolerability in a real-world setting. METHODS: We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases for real-world studies published up to March 3, 2023, on pirfenidone and nintedanib for idiopathic pulmonary fibrosis. RESULTS: A total of 74 studies with 23,119 participants were included. After 12 months of treatment, the change from baseline in percent predicted FVC (%FVC) was - 0.75% for pirfenidone and - 1.43% for nintedanib. The change from baseline in percent predicted DLCO (%DCLO) was - 2.32% for pirfenidone and - 3.95% for nintedanib. The incidence of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) was 12.5% for pirfenidone and 14.4% for nintedanib. The IPF-related mortality rates of pirfenidone and nintedanib were 13.4% and 7.2%, respectively. The all-cause mortality was 20.1% for pirfenidone and 16.6% for nintedanib. In the pirfenidone group, 16.6% of patients discontinued treatment because of adverse events, and in the nintedanib group, 16.2% of patients discontinued treatment because of adverse events. The incidence of adverse events was 56.4% and 69.7% for pirfenidone and nintedanib, respectively. CONCLUSION: The results of this study indicate that pirfenidone and nintedanib are both effective in slowing down the decline of lung function in IPF patients in real-world settings. The incidence of adverse events with pirfenidone is lower than that with nintedanib, but both are below the clinical trial data, and no new major adverse events have been observed. The discontinuation rates due to adverse reactions of the two drugs are consistent with clinical trial data, indicating good tolerability. However, the mortality rates and AE-IPF incidence rates of these two drugs in real-world settings are higher than those in previous clinical trials, with pirfenidone patients showing a higher mortality rate. Further large-sample studies are needed to investigate the risks of these drugs in these aspects. Additionally, we recommend that future real-world studies pay more attention to patients' subjective symptoms and conduct stratified analyses of the efficacy and safety of pirfenidone and nintedanib based on factors such as patients' baseline lung function, comorbidities, and age, in order to provide more personalized medication advice for IPF patients in clinical practice.
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BACKGROUND: Older adults are at high risk of femoral neck fractures (FNFs). Elderly patients face and adapt to significant psychological burdens, resulting in different degrees of psychological stress response. Total hip replacement is the preferred treatment for FNF in elderly patients; however, some patients have poor postoperative prognoses, and the underlying mechanism is unknown. We speculated that the postoperative prognosis of elderly patients with FNF may be related to preoperative psychological stress. AIM: To explore the relationship between preoperative psychological stress and the short-term prognosis of elderly patients with FNF. METHODS: In this retrospective analysis, the baseline data, preoperative 90-item Symptom Checklist score, and Harris score within 6 months of surgery of 120 elderly patients with FNF who underwent total hip arthroplasty were collected. We analyzed the indicators of poor short-term postoperative prognosis and the ability of the indicators to predict poor prognosis and compared the correlation between the indicators and the Harris score. RESULTS: Anxiety, depression, garden classification of FNF, cause of fracture, FNF reduction quality, and length of hospital stay were independent influencing factors for poor short-term postoperative prognoses in elderly patients with FNF (P < 0.05). The areas under the curve for anxiety, depression, and length of hospital stay were 0.742, 0.854, and 0.749, respectively. The sensitivities of anxiety, depression, garden classification of FNF, and prediction of the cause of fracture were 0.857, 0.786, 0.821, and 0.821, respectively. The specificities of depression, FNF quality reduction, and length of hospital stay were the highest at 0.880, 0.783, and 0.761, respectively. Anxiety, depression, and somatization scores correlated moderately with Harris scores (r = -0.523, -0.625, and -0.554; all P < 0.001). CONCLUSION: Preoperative anxiety, depression, and somatization are correlated with poor short-term prognosis in elderly patients with FNF and warrant consideration.
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BACKGROUND: We report a case of eye-penetrating injury in which a massive silicone oil migration into the patient's subconjunctival space and orbit occurred after vitrectomy. CASE SUMMARY: A 30-year-old male patient sought medical attention at Ganzhou People's Hospital after experiencing pain and vision loss in his left eye due to a nail wound on December 9, 2023. Diagnosis of penetrating injury caused by magnetic foreign body retention in the left eye and hospitalization for treatment. On December 9, 2023, pars plana vitrectomy was performed on the left eye for intraocular foreign body removal, abnormal crystal extraction, retinal photocoagulation. Owing to the discovery of retinal detachment at the posterior pole during surgery, silicone oil was injected to fill the vitreous body, following which upper conjunctival bubble-like swelling was observed. Postoperative orbital computed tomography (CT) review indicated migration of silicone oil to the subconjunctival space and orbit through a self-permeable outlet. On December 18, 2023, the patient sought treatment at the First Affiliated Hospital of Nanchang University, China. The patient presented with a pronounced foreign body sensation following left eye surgery. On December 20, 2023, the foreign body was removed from the left eye frame and an intraocular examination was conducted. The posterior scleral tear had closed, leading to termination of the surgical procedure following supplementary laser treatment around the tear. The patient reported a significant reduction in ocular surface symptoms just one day after surgery. Furthermore, a notable decrease in the migration of silicone oil was observed in orbital CT scans. CONCLUSION: The timing of silicone oil injection for an eye-penetrating injury should be carefully evaluated to avoid the possibility of silicone oil migration.
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Despite advancements in treatment, approximately 25% of breast cancer patients experience long-term skeletal muscle wasting (SMW), which limits mobility, reduces drug tolerance and adversely impacts survival. By understanding the underlying molecular mechanisms of SMW, we may develop new strategies to alleviate this condition and improve the lives of breast cancer patients. Chemokines are small soluble factors that regulate homing of immune cells to tissues during inflammation. In breast cancers, overexpression of the C-C chemokine ligand 2 (CCL2) correlates with unfavorable prognosis. Elevated levels of CCL2 in peripheral blood indicate possible systemic effects of this chemokine in breast cancer patients. Here, we investigated the role of CCL2 signaling on SMW in a tumor and non-tumor context. In vitro, increasing concentrations of CCL2 inhibits myoblast and myotube function through C-C chemokine receptor 2 (CCR2) dependent mechanisms involving JNK, SMAD3 and AMPK signaling. In healthy mice, delivery of recombinant CCL2 protein promotes SMW in a dose dependent manner. In vivo knockdown of breast tumor derived CCL2 partially protects against SMW. Overall, chronic, upregulated CCL2/CCR2 signaling positively regulates SMW, with implications on therapeutic targeting.
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Phytochemical investigation on the extract of the seeds of Thevetia peruviana resulted in the isolation of six new cardiac glycosides, namely theveperosides A-F (1-6), including a rare 19-nor-cardenolide (1), together with seven known analogues (7-13). The chemical structures of these compounds were determined based on detailed spectroscopic analysis. The cytotoxic activities of 1-13 were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cell lines, and their structure-activity relationships (SARs) were investigated. Compound 3 exhibited the significant cytotoxic effects with IC50 values ranging from 0.032 to 0.055 µΜ, which could induce HepG2 cells apoptosis in a dose-dependent manner.
Subject(s)
Antineoplastic Agents, Phytogenic , Cardiac Glycosides , Phytochemicals , Seeds , Thevetia , Humans , Cardiac Glycosides/pharmacology , Cardiac Glycosides/isolation & purification , Cardiac Glycosides/chemistry , Seeds/chemistry , Molecular Structure , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Thevetia/chemistry , Structure-Activity Relationship , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Apoptosis/drug effectsABSTRACT
AIM: Recent imaging studies have found significant abnormalities in the brain's functional or structural connectivity among patients with high myopia (HM), indicating a heightened risk of cognitive impairment and other behavioral changes. However, there is a lack of research on the topological characteristics and connectivity changes of the functional networks in HM patients. In this study, we employed graph theoretical analysis to investigate the topological structure and regional connectivity of the brain function network in HM patients. METHODS: We conducted rs-fMRI scans on 82 individuals with HM and 59 healthy controls (HC), ensuring that the two groups were matched for age and education level. Through graph theoretical analysis, we studied the topological structure of whole-brain functional networks among participants, exploring the topological properties and differences between the two groups. RESULTS: In the range of 0.05 to 0.50 of sparsity, both groups demonstrated a small-world architecture of the brain network. Compared to the control group, HM patients showed significantly lower values of normalized clustering coefficient (γ) (P = 0.0101) and small-worldness (σ) (P = 0.0168). Additionally, the HM group showed lower nodal centrality in the right Amygdala (P < 0.001, Bonferroni-corrected). Notably, there is an increase in functional connectivity (FC) between the saliency network (SN) and Sensorimotor Network (SMN) in the HM group, while the strength of FC between the basal ganglia is relatively weaker (P < 0.01). CONCLUSION: HM Patients exhibit reduced small-world characteristics in their brain networks, with significant drops in γ and σ values indicating weakened global interregional information transfer ability. Not only that, the topological properties of the amygdala nodes in HM patients significantly decline, indicating dysfunction within the brain network. In addition, there are abnormalities in the FC between the SN, SMN, and basal ganglia networks in HM patients, which is related to attention regulation, motor impairment, emotions, and cognitive performance. These findings may provide a new mechanism for central pathology in HM patients.
Subject(s)
Brain , Magnetic Resonance Imaging , Nerve Net , Humans , Male , Female , Adult , Magnetic Resonance Imaging/methods , Brain/physiopathology , Brain/diagnostic imaging , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Young Adult , Brain Mapping/methods , Myopia, Degenerative/physiopathology , Rest/physiologyABSTRACT
Understanding the alterations in soil microbial communities in response to climate warming and their controls over soil carbon (C) processes is crucial for projecting permafrost C-climate feedback. However, previous studies have mainly focused on microorganism-mediated soil C release, and little is known about whether and how climate warming affects microbial anabolism and the subsequent C input in permafrost regions. Here, based on a more than half-decade of in situ warming experiment, we show that compared with ambient control, warming significantly reduces microbial C use efficiency and enhances microbial network complexity, which promotes soil heterotrophic respiration. Meanwhile, microbial necromass markedly accumulates under warming likely due to preferential microbial decomposition of plant-derived C, further leading to the increase in mineral-associated organic C. Altogether, these results demonstrate dual roles of microbes in affecting soil C release and stabilization, implying that permafrost C-climate feedback would weaken over time with dampened response of microbial respiration and increased proportion of stable C pool.
Subject(s)
Carbon , Permafrost , Soil Microbiology , Soil , Carbon/metabolism , Soil/chemistry , Permafrost/microbiology , Global Warming , Carbon Cycle , Microbiota/physiology , Climate ChangeABSTRACT
BACKGROUND: A growing number of studies have demonstrated that the polar regions have the potential to be a significant repository of microbial resources and a potential source of active ingredients. Genome mining strategy plays a key role in the discovery of bioactive secondary metabolites (SMs) from microorganisms. This work highlighted deciphering the biosynthetic potential of an Arctic marine-derived strain Aspergillus sydowii MNP-2 by a combination of whole genome analysis and antiSMASH as well as feature-based molecular networking (MN) in the Global Natural Products Social Molecular Networking (GNPS). RESULTS: In this study, a high-quality whole genome sequence of an Arctic marine strain MNP-2, with a size of 34.9 Mb was successfully obtained. Its total number of genes predicted by BRAKER software was 13,218, and that of non-coding RNAs (rRNA, sRNA, snRNA, and tRNA) predicted by using INFERNAL software was 204. AntiSMASH results indicated that strain MNP-2 harbors 56 biosynthetic gene clusters (BGCs), including 18 NRPS/NRPS-like gene clusters, 10 PKS/PKS-like gene clusters, 8 terpene synthse gene clusters, 5 indole synthase gene clusters, 10 hybrid gene clusters, and 5 fungal-RiPP gene clusters. Metabolic analyses of strain MNP-2 grown on various media using GNPS networking revealed its great potential for the biosynthesis of bioactive SMs containing a variety of heterocyclic and bridge-ring structures. For example, compound G-8 exhibited a potent anti-HIV effect with an IC50 value of 7.2 nM and an EC50 value of 0.9 nM. Compound G-6 had excellent in vitro cytotoxicities against the K562, MCF-7, Hela, DU145, U1975, SGC-7901, A549, MOLT-4, and HL60 cell lines, with IC50 values ranging from 0.10 to 3.3 µM, and showed significant anti-viral (H1N1 and H3N2) activities with IC50 values of 15.9 and 30.0 µM, respectively. CONCLUSIONS: These findings definitely improve our knowledge about the molecular biology of genus A. sydowii and would effectively unveil the biosynthetic potential of strain MNP-2 using genomics and metabolomics techniques.
Subject(s)
Aspergillus , Multigene Family , Aspergillus/genetics , Aspergillus/metabolism , Arctic Regions , Humans , Biological Products/metabolism , Aquatic Organisms/genetics , Aquatic Organisms/metabolism , Cell Line, Tumor , Biosynthetic Pathways/genetics , Secondary Metabolism/genetics , Genome, FungalABSTRACT
Replacing corn with different levels of wheat in the iso-energy and -protein diet of broilers and the impacts on growth performance and intestinal homeostasis of broilers under the condition of supplying the multienzyme complex were evaluated in this study. A total of 480 10-day-old male broilers were assigned randomly to the low-level wheat group (15% wheat and 35.18% corn), the medium-level wheat group (30% and 22.27%), and the high-level wheat group (55.77% wheat without corn) until 21 d. The different levels of wheat supplementation did not affect hepatic function, serum glycolipid profile, or bone turnover. The replacement of corn with 55% wheat in the diet of broilers increased the body weight at 21 d and feed intake during 10 to 21 d (both p < 0.05), with a comparable feed conversion ratio. Compared with the low-wheat group, the dietary addition of medium or high wheat levels notably increased the ratio of villus height to crypt depth in the duodenum (p < 0.05) and the ileal villus height (p < 0.05). Meanwhile, the supplementation of medium and high wheat in the diet increased the proportion of Bacteroidetes, and a diet with high wheat proportion elevated the content of Firmicutes when compared to the low-level wheat group (both p < 0.05). In addition, the diet containing 30-55% wheat enhanced the anti-inflammatory capability in both the ileum and the serum. These findings suggest that the replacement of corn with 55% wheat in the diet improved the growth performance of 21-day-old broilers, which might be linked to the alteration in intestinal morphology and cecal microbiota.
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Subclinical hypothyroidism (SCH) in pregnancy is the most common form of thyroid dysfunction in pregnancy, which can affect fetal nervous system development and increase the risk of neurodevelopmental disorders after birth. However, the mechanism of the effect of maternal subclinical hypothyroidism on fetal brain development and behavioral phenotypes is still unclear and requires further study. In this study, we constructed a mouse model of maternal subclinical hypothyroidism by exposing dams to drinking water containing 50 ppm propylthiouracil (PTU) during pregnancy and found that its offspring were accompanied by severe cognitive deficits by behavioral testing. Mechanistically, gestational SCH resulted in the upregulation of protein expression and activity of HDAC1/2/3 in the hippocampus of the offspring. ChIP analysis revealed that H3K9ac on the neurogranin (Ng) promoter was reduced in the hippocampus of the offspring of SCH, with a significant reduction in Ng protein, leading to reduced expression levels of synaptic plasticity markers PSD95 (a membrane-associated protein in the postsynaptic density) and SYN (synaptophysin, a specific marker for presynaptic terminals), and impaired synaptic plasticity. In addition, administration of MS-275 (an HDAC1/2/3-specific inhibitor) to SCH offspring alleviated impaired synaptic plasticity and cognitive dysfunction in offspring. Thus, our study suggests that maternal subclinical hypothyroidism may mediate offspring cognitive dysfunction through the HDAC1/2/3-H3K9ac-Ng pathway. Our study contributes to the understanding of the signaling mechanisms underlying maternal subclinical hypothyroidism-mediated cognitive impairment in the offspring.
Subject(s)
Cognitive Dysfunction , Histone Deacetylase 1 , Histone Deacetylase 2 , Hypothyroidism , Neurogranin , Prenatal Exposure Delayed Effects , Animals , Neurogranin/metabolism , Neurogranin/genetics , Hypothyroidism/metabolism , Female , Pregnancy , Mice , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/etiology , Histone Deacetylase 2/metabolism , Histone Deacetylase 2/genetics , Prenatal Exposure Delayed Effects/metabolism , Histone Deacetylase 1/metabolism , Histone Deacetylase 1/genetics , Down-Regulation , Hippocampus/metabolism , Male , Histone Deacetylases/metabolism , Histone Deacetylases/genetics , Mice, Inbred C57BL , Neuronal PlasticityABSTRACT
Recent studies have highlighted the potential of Saccharina japonica Polysaccharides (SJPs) in alleviating high-fat diet (HFD)-induced obesity by regulating gut microbiota, which warrants further exploration to elucidate the underlying structure-activity relationship. In this study, five polysaccharide fractions (Sj-T, Sj-T-1, Sj-T-2, Sj-T-3, and Sj-T-4) with different structure characteristics were prepared from S. japonica, and their effects on HFD-induced obesity and gut microbiota composition were investigated using C57BL/6J mice. The results revealed that oral administration of Sj-T considerably suppressed HFD-induced obesity, glucose metabolic dysfunction, and other disordered symptoms. While, Sj-T-2, which has the lowest molecular weight, was the most effective in alleviating HFD-induced obesity and had the second-best effect on improving HFD-induced impaired glucose tolerance among the five SJPs. Supplementation with SJPs significantly modulated HFD-induced gut microbiota dysbiosis both at the phylum and species levels, such as enriching Desulfobacterota and Actinobacteriota, while suppressing the abundance of Bacteroidota. Sj-T also dramatically restored the gut microbiota composition by modulating the abundance of many crucial gut bacterial taxa, including s_Bacteroides_acidifaciens, s_Lachnospiraceae _bacterium, and g_Lachnospiraceae_NK4A136_group. Besides, SJPs also dramatically altered the function of gut microbiota, including many carbohydrate-metabolism enzymes. This study highlights the potential of SJPs in preventing obesity and restoring intestinal homeostasis in obese individuals.
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In this paper, we proposed an axially slow-variation microbubble resonator fabricated by an improved arc discharge method and applied to axial strain sensing. The prepared resonators are characterized by ultra-thin wall thickness and axial slow-variation. The wall thickness was experimentally measured to reach 938â nm and maintain a quality factor of an optical mode as large as 7.36 ×107. The main factors affecting the strain sensitivity of the microbubble resonators are investigated theoretically and experimentally. Experimentally, the maximum sensitivity measured was 13.08pm/µÎµ, which is three times higher than the microbubble resonators without this method. The device is simple to prepare and possesses ultra-thin wall thickness. It is promising for applications in high-precision sensing, such as single molecule and biological sensing.
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BACKGROUND This prospective study from a single center aimed to compare the perioperative blood loss (PBL) in 79 patients with intertrochanteric fractures (IF) treated with intramedullary nailing (IMN) using 3 regimens of combined tranexamic acid (TXA) and low molecular weight heparin (LMWH), proposing a novel therapy of 4-dose TXA. MATERIAL AND METHODS We recruited 79 patients and randomly divided them into 3 groups. The 4-dose TXA group (22 patients) received 1.0 g intravenous TXA 30 min before surgery and 1.0 g at intervals of 3, 6, and 9 h before surgery. The 1-dose TXA group (25 patients) received 1.0 g intravenous TXA 30 min before surgery, while the control group (32 patients) did not receive TXA. LMWH was applied 12 h after surgery in each group. The primary metrics evaluated included hidden blood loss (HBL), total blood loss (TBL), and the number and incidence rate of deep vein thrombosis (DVT). RESULTS Analysis of the HBL revealed that the 4-dose TXA group had the lowest average (583.13±318.08 ml), followed by the 1-dose TXA group (902.94±509.99 ml), and the control group showed the highest (1154.39±452.06 ml) (P<0.05). A similar result was observed for TBL (4-dose group: 640.86±337.22 ml, 1-dose group: 971.74±511.14 ml, control group: 1226.27±458.22 ml, P<0.05). Regarding DVT, the 4-dose TXA group had 5 cases (incidence rate 22.73%), the 1-dose TXA group had 6 cases (incidence rate 24.00%), and the control group had 8 cases (incidence rate 25.00%), with no significant difference among groups (P>0.05). CONCLUSIONS Treatment using 4-dose TXA and LMWH can effectively reduce PBL without increasing the DVT risk in IF patients with IMN.
Subject(s)
Blood Loss, Surgical , Heparin, Low-Molecular-Weight , Hip Fractures , Tranexamic Acid , Venous Thrombosis , Humans , Tranexamic Acid/administration & dosage , Tranexamic Acid/therapeutic use , Female , Male , Hip Fractures/surgery , Heparin, Low-Molecular-Weight/administration & dosage , Heparin, Low-Molecular-Weight/therapeutic use , Aged , Blood Loss, Surgical/prevention & control , Venous Thrombosis/drug therapy , Venous Thrombosis/prevention & control , Prospective Studies , Middle Aged , Perioperative Care/methods , Antifibrinolytic Agents/administration & dosage , Antifibrinolytic Agents/therapeutic use , Aged, 80 and over , Fracture Fixation, Intramedullary/methods , Fracture Fixation, Intramedullary/adverse effectsABSTRACT
Low Molecular Weight Heparins (LMWHs) are well-established for use in the prevention and treatment of thrombotic diseases, and as a substitute for unfractionated heparin (UFH) due to their predictable pharmacokinetics and subcutaneous bioavailability. LMWHs are produced by various depolymerization methods from UFH, resulting in heterogeneous compounds with similar biochemical and pharmacological properties. However, the delicate supply chain of UFH and potential contamination from animal sources require new manufacturing approaches for LMWHs. Various LMWH preparation methods are emerging, such as chemical synthesis, enzymatic or chemical depolymerization and chemoenzymatic synthesis. To establish the sameness of active ingredients in both innovator and generic LMWH products, the Food and Drug Administration has implemented a stringent scientific method of equivalence based on physicochemical properties, heparin source material and depolymerization techniques, disaccharide composition and oligosaccharide mapping, biological and biochemical properties, and in vivo pharmacodynamic profiles. In this review, we discuss currently available LMWHs, potential manufacturing methods, and recent progress for manufacturing quality control of these LMWHs.