Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

Trimethylamine-N-oxide aggravated the sympathetic excitation in D-galactose induced aging rats by down-regulating P2Y12 receptor in microglia.

This study aimed to determine whether trimethylamine N-oxide (TMAO) was involved in sympathetic activation in aging and the underlying mechanisms. Our hypothesis is TMAO reduces P2Y12 receptor (P2Y12R) and induces microglia-mediated inflammation in the paraventricular nucleus (PVN), then leading to sympathetic activation in aging. This study involved 18 young adults and 16 old adults. Aging rats were established by injecting D-galactose (D-gal, 200 mg/kg/d) subcutaneously for 12 weeks. TMAO (120 mg/kg/d) or 1% 3, 3-dimethyl-l-butanol (DMB) was administrated via drinking water for 12 weeks to investigate their effects on neuroinflammation and sympathetic activation in aging rats. Plasma TMAO, NE and IL-1ß levels were higher in old adults than in young adults. In addition, standard deviation of all normal to normal intervals (SDNN) and standard deviation of the average of normal to normal intervals (SDANN) were lower in old adults and negatively correlated with TMAO, indicating sympathetic activation in old adults, which is associated with an increase in TMAO levels. Treatment of rats with D-gal showed increased senescence-associated protein levels and microglia-mediated inflammation, as well as decreased P2Y12R protein levels in PVN. Plasma TMAO, NE and IL-1ß levels were increased, accompanied by enhanced renal sympathetic nerve activity (RSNA). While TMAO treatment exacerbated the above phenomenon, DMB mitigated it. These findings suggest that TMAO contributes to sympathetic hyperactivity in aging by downregulating P2Y12R in microglia and increasing inflammation in the PVN. These results may provide promising new target for the prevention and treatment of aging and aging-related diseases.

RELN gene-related drug-resistant epilepsy with periventricular nodular heterotopia treated with radiofrequency thermocoagulation: a case report.

An increasing number of gene mutations associated with epilepsy have been identified, some linked to gray matter heterotopia-a common cause of drug-resistant epilepsy. Current research suggests that gene mutation-associated epilepsy should not be considered a contraindication for surgery in epilepsy patients. At present, stereoelectroencephalography-guided radiofrequency thermocoagulation is an important method to treat periventricular nodular heterotopia-associated drug-resistant epilepsy. We present a case of drug-resistant epilepsy, accompanied by periventricular nodular heterotopia and a heterozygous mutation of the RELN gene, successfully treated with radiofrequency thermocoagulation, resulting in a favorable outcome.

HyperColorization: propagating spatially sparse noisy spectral clues for reconstructing hyperspectral images.

Hyperspectral cameras face challenging spatial-spectral resolution trade-offs and are more affected by shot noise than RGB photos taken over the same total exposure time. Here, we present a colorization algorithm to reconstruct hyperspectral images from a grayscale guide image and spatially sparse spectral clues. We demonstrate that our algorithm generalizes to varying spectral dimensions for hyperspectral images, and show that colorizing in a low-rank space reduces compute time and the impact of shot noise. To enhance robustness, we incorporate guided sampling, edge-aware filtering, and dimensionality estimation techniques. Our method surpasses previous algorithms in various performance metrics, including SSIM, PSNR, GFC, and EMD, which we analyze as metrics for characterizing hyperspectral image quality. Collectively, these findings provide a promising avenue for overcoming the time-space-wavelength resolution trade-off by reconstructing a dense hyperspectral image from samples obtained by whisk or push broom scanners, as well as hybrid spatial-spectral computational imaging systems.

Circulating tumour DNA dynamics during alternating chemotherapy and hormonal therapy in metastatic breast cancer: the ALERT study.

PURPOSE: Although changes in circulating tumour DNA (ctDNA) in breast cancer are well described, the kinetics of their fluctuations has not been described over short timescales. We investigated ctDNA dynamics during alternating cycles of chemotherapy and hormonal treatment in pre-treated patients with oestrogen receptor-positive metastatic breast cancer. METHODS: Patients received alternating, 9-week cycles of eribulin and aromatase inhibitors (AIs). The clinical primary endpoint, progression-free survival (PFS), was monitored at 3, 6 and 9 months; secondary endpoints, clinical benefit rate (CBR), safety and tolerability profiles, were also assessed. Importantly, ctDNA fluctuations were monitored using the Oncomine™ Breast cfDNA assay to test whether biomarkers may change rapidly between chemotherapy and aromatase inhibitor (AI) treatment in the setting of advanced breast cancer, potentially reflecting disease dynamics. RESULTS: The median PFS was 202 days (95% CI: 135-undefined) and 235 days (95% CI: 235-undefined) at 6 and 9 months, respectively, with a 50% CBR at both 6 and 9 months. Dynamic changes in ctDNA were observed in short timescales between chemotherapy and AI treatment and support the clinical benefit (CB) seen in individual patients and, critically, appear informative of acquired resistance in real time. CONCLUSION: Changes in ctDNA can occur rapidly and reflect changes in patients' clinical tumour responses (NCT02681523).

Guiding function of positron emission tomography-computed tomography examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma.

AIM: To explore the role of positron emission tomography-computed tomography (PET-CT) examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma (OAML). METHODS: The general clinical data, postoperative PET-CT results, treatment regimens, and the prognosis of 21 histopathologically confirmed OAML patients between October 2017 and September 2021 were collected. Among the 21 patients, five patients underwent surgical treatment alone, 13 patients underwent surgical treatment combined with radiotherapy, and three patients underwent surgical treatment combined with chemotherapy. RESULTS: The follow-up period ranged from 8 to 79mo, with four cases of recurrence and no deaths. Through PET-CT examination, two patients exhibited both local ocular metabolic elevation and systemic metastasis, and one of these patients had cervical lymph node metastasis, while the other had submandibular and parotid gland metastasis. Nine patients showed only local ocular metabolic elevation, while 10 patients had no abnormal metabolic activity locally. CONCLUSION: PET-CT examination plays a crucial role in detecting residual lesions and recurrence following tumor resection, aiding in precise disease staging, and facilitating the development of personalized treatment plans, ultimately improving patient prognosis.

Analysis of Phase Mismatch for Mercurous Bromide-Based Non-Collinear AOTF Design in Spectral Imaging Applications.

The spectral and spatial characteristics of Acousto-Optic Tunable Filters (AOTFs), such as a tuning curve, spectral resolution, angular aperture, and diffraction efficiency, are determined by the device's acousto-optic crystal configuration and piezoelectric transducer. For high-throughput spectral imaging applications, it is essential to enlarge the spectral bandwidth and angular aperture during the design phase of AOTFs. Thus, phase mismatch due to incident angle or wavelength was studied analytically using phase diagrams in this paper. Additionally, a performance parameter analysis model was established based on the use of mercurous bromide crystals for large angular aperture AOTF device design, and the impact of crystal and transducer design parameters on the spectral bandwidth and angular aperture was evaluated. This also experimentally validates the diffraction capability of AOTFs made from mercurous bromide crystal, which possess a broad spectral transmission ability ranging from visible to long-wave infrared.

Naps and cardiovascular disease risk in different age and sex groups: evidence from a large community cohort.

STUDY OBJECTIVES: This study examined the relationship between naps and cardiovascular disease (CVD) events or death in different age and sex groups. METHODS: A total of 3069 participants stratified by age (<65, 65-74, and ≥75 years old) and sex, underwent Cox regression analysis to assess nap's impact on CVD risk. Restricted cubic spline plots (RCS) were used for dose-response relationships. RESULTS: Significant age-stratified interactions were found when exploring the associations between nap frequency or duration and CVD events (P interaction = 0.001, 0.036 respectively). Individuals younger than 65 years with higher nap frequency or longer nap duration had a significantly increased risk of CVD events (P < 0.001, P = 0.001 respectively). The age group of 65-74 years showed significant associations between CVD events and nap frequency or nap duration (P = 0.017, 0.016 respectively), together with nap duration and CVD deaths (P = 0.008). In the subgroup of females aged 65-74, significant associations were found between nap frequency or duration and CVD events (P = 0.006, 0.002 respectively). Nap frequency or duration was also significantly associated with CVD deaths (P =0.005, 0.010 respectively). CONCLUSIONS: This study underscores a noteworthy correlation between a higher frequency or longer duration of daytime nap and an increased susceptibility to CVD among individuals aged 65-74 years, particularly in females. However, further research is needed to better understand the underlying mechanisms.

Record High Iodate Anion Capture by a Redox-Active Cationic Polymer Network.

As a critical radioactive anionic contaminant, traditional adsorbents primarily remove iodate (IO3-) through ion exchange or hard acid-hard base interactions, but suffer from limited affinity and capacity. Herein, employing the synergistic effect of ion exchange and redox, we successfully synthesized a redox-active cationic polymer network (SCU-CPN-6, [C9H10O2N5•Cl]n) by merging guanidino groups with ion-exchange capability and phenolic groups with redox ability via a Schiff base reaction. SCU-CPN-6 exhibits a groundbreaking adsorption capacity of 896 mg/g for IO3-. The inferior adsorption capacities of polymeric networks containing only redox (~0 mg/g) or ion exchange (232 mg/g) fragments underscore the synergistic "1 + 1 > 2" effect of the two mechanisms. Besides, SCU-CPN-6 shows excellent uptake selectivity for IO3- in the presence of high concentrations of SO42-, Cl-, and NO3-. Meanwhile, a high distribution coefficient indicates its exemplary deep-removal performance for low IO3- concentration. The synergic strategy not only presents a breakthrough solution for the efficient removal of IO3- but also establishes a promising avenue for the design of advanced adsorbents for diverse applications.

Efficiency and Durability of EIVOM on Acute Reconnection After Mitral Isthmus Bidirectional Block.

BACKGROUND: Reconnection after mitral isthmus (MI) block with radiofrequency ablation is common. OBJECTIVES: The aim of this study was to investigate the effects of ethanol infusion in the vein of Marshall (EIVOM) on acute reconnection after MI bidirectional block. METHODS: Patients with persistent atrial fibrillation who were scheduled to receive radiofrequency ablation for the first time were randomly assigned to the radiofrequency catheter ablation (RFCA) group (n = 44) or the EIVOM group (n = 45). The RFCA group's strategy was bilateral pulmonary vein ablation and linear ablation; in the EIVOM group, EIVOM was performed first. The primary endpoint was acute reconnection 30 minutes after MI bidirectional block. RESULTS: A total of 89 patients (average age 62.9 years; 57.3% male) were enrolled. The average duration for persistent atrial fibrillation was 2.3 years. Before observation, all patients in the EIVOM group achieved MI bidirectional block (45 of 45 [100%]), compared with 84.1% (37 of 44) in the RFCA group. After the observation, 3 cases of MI reconnection occurred in the EIVOM group and 13 cases in the RFCA group (6.7% vs 35.1%; P < 0.05). After additional ablation, the final MI block rates in the EIVOM and RFCA groups were 97.8% (44 of 45) and 72.7% (32 of 44), respectively. During a 1-year follow-up, 8 of 45 patients who underwent EIVOM had recurrent atrial fibrillation, compared with 14 of 44 in the RFCA group (17.8% vs 31.8%; P < 0.01). CONCLUSIONS: EIVOM can reduce acute reconnection after MI bidirectional block and significantly increase first-pass MI block.

Association between PEMT rs7946 and blood pressure levels in Chinese adolescents.

OBJECTIVES: This study was to explore blood pressure levels in Chinese adolescents with different genotypes of phosphatidylethanolamine N-methyltransferase (PEMT) gene (PEMT) rs7946, as well as effects of dietary intake on blood pressure levels with different genders and different genotypes of PEMT rs7946. METHODS: PEMT rs7946 genotypes were identified by PCR-restriction fragment length polymorphism and verified by DNA sequencing. Blood pressure was measured using a standard mercury sphygmomanometer. Dietary intakes were analyzed based on a 3-day diet diary, and dietary components were calculated using computer software. RESULTS: A total of 721 high school students (314 males and 407 females) at the age of 16.86 ±â€…0.59 years were included. The A allele carriers of PEMT rs7946 had increased levels of SBP, DBP, mean arterial pressure (MAP) and pulse pressure (PP) than the GG homozygotes in the female subjects. There were significant interactions between PEMT rs7946 and gender on SBP and MAP levels, regardless of whether an unadjusted or adjusted model was used. When dietary intake was taken into account, fat intake was positively associated with SBP and PP in the male GG homozygotes, while protein intake was positively associated with PP in the female A allele carriers of PEMT rs7946. CONCLUSION: This study suggests that PEMT rs7946 is significantly associated with blood pressure levels in human being. There might be interactions among PEMT rs7946, gender, and dietary intake on blood pressure levels in the adolescent population.

Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as novel HIV-1 integrase strand transfer inhibitors.

Integrase plays an important role in the life cycle of HIV-1, and integrase strand transfer inhibitors (INSTIs) can effectively impair the viral replication. However, drug resistance mutations have been confirmed to decrease the efficacy of INSTI during the antiviral therapy. Herein, indole-2-carboxylic acid (1) was found to inhibit the strand transfer of integrase, and the indole nucleus of compound 1 was observed to chelate with two Mg2+ ions within the active site of integrase. Through optimization of compound 1, a series of indole-2-carboxylic acid derivatives were designed and synthesized, and compound 17a was proved to markedly inhibit the effect of integrase, with IC50 value of 3.11 µM. Binding mode analysis of 17a demonstrated that the introduced C6 halogenated benzene ring could effectively bind with the viral DNA (dC20) through π-π stacking interaction. These results indicated that indole-2-carboxylic acid is a promising scaffold for the development of integrase inhibitors.

Low-Pressure Pancake Bouncing on Superhydrophobic Surfaces.

A new form of pancake bouncing is discovered in this work when a droplet impacts onto micro-structured superhydrophobic surfaces in an environment pressure less than 2 kPa, and an unprecedented reduction of contact time by ≈85% is obtained. The mechanisms of forming this unique phenomenon are examined by combining experimental observation, numeical modelling and an improved theoretical model for the overpressure effect arising from the vaporisation inside micro-scaled structures. The competition among the vapor overpressure effect, the droplet impact force, and the surface adhesion determines if the pancake bouncing behavior could occur. After the lift-off the lamella, the pancake bouncing is initiated and its subsequent dynamics is controlled by the internal momentum transfer. Complementary to the prior studies, this work enriches the knowledge of droplet dynamics in low pressure, which allows new strategies of surface morphology engineering for droplet control, an area of high importance for many engineering applications.

Heparin-enriched plasma proteome is significantly altered in Alzheimer's Disease.

Introduction: Heparin binding proteins (HBPs) with roles in extracellular matrix assembly are strongly correlated to ß-amyloid (Aß) and tau pathology in Alzheimer's disease (AD) brain and cerebrospinal fluid (CSF). However, it remains challenging to detect these proteins in plasma using standard mass spectrometry-based proteomic approaches. Methods: We employed heparin affinity chromatography, followed by off-line fractionation and tandem mass tag mass spectrometry (TMT-MS), to capture and enrich HBPs in plasma obtained from AD (n=62) and control (n=47) samples. These profiles were then correlated to a consensus AD brain proteome, as well as with Aß, tau and phosphorylated tau (pTau) CSF biomarkers from the same individuals. We then leveraged published human postmortem brain proteome datasets to assess the overlap with the heparin-enriched plasma proteome. Results: Heparin-enrichment from plasma was highly reproducible, enriched well-known HBPs like APOE and thrombin, and depleted high-abundance proteins such as albumin. A total of 2865 proteins, spanning 10 orders of magnitude were detectable. Utilizing a consensus AD brain protein co-expression network, we observed that specific plasma HBPs exhibited consistent direction of change in both brain and plasma, whereas others displayed divergent changes highlighting the complex interplay between the two compartments. Elevated HBPs in AD plasma, when compared to controls, included members of the matrisome module in brain that accumulate within Aß deposits, such as SMOC1, SMOC2, SPON1, MDK, OLFML3, FRZB, GPNMB, and APOE. Additionally, heparin enriched plasma proteins demonstrated significant correlations with conventional AD CSF biomarkers, including Aß, total tau, pTau, and plasma pTau from the same individuals. Conclusion: These findings support the utility of a heparin-affinity approach for enriching amyloid-associated proteins, as well as a wide spectrum of plasma biomarkers that reflect pathological changes in the AD brain.

Decreased levels of hydrogen sulfide in the hypothalamic paraventricular nucleus contribute to sympathetic hyperactivity induced by cerebral infarction.

Paroxysmal sympathetic hyperactivity (PSH) is a common clinical feature secondary to ischemic stroke (IS), but its mechanism is poorly understood. We aimed to investigate the role of H2S in the pathogenesis of PSH. IS patients were divided into malignant (MCI) and non-malignant cerebral infarction (NMCI) group. IS in rats was induced by the right middle cerebral artery occlusion (MCAO). H2S donor (NaHS) or inhibitor (aminooxy-acetic acid, AOAA) were microinjected into the hypothalamic paraventricular nucleus (PVN). Compared with the NMCI group, patients in the MCI group showed PSH, including tachycardia, hypertension, and more plasma norepinephrine (NE) that was positively correlated with levels of creatine kinase, glutamate transaminase, and creatinine respectively. The 1-year survival rate of patients with high plasma NE levels was lower. The hypothalamus of rats with MCAO showed increased activity, especially in the PVN region. The levels of H2S in PVN of the rats with MCAO were reduced, while the blood pressure and renal sympathetic discharge were increased, which could be ameliorated by NaHS and exacerbated by AOAA. NaHS completely reduced the disulfide bond of NMDAR1 in PC12 cells. The inhibition of NMDAR by MK-801 microinjected in PVN of rats with MCAO also could lower blood pressure and renal sympathetic discharge. In conclusion, PSH may be associated with disease progression and survival in patients with IS. Decreased levels of H2S in PVN were involved in regulating sympathetic efferent activity after cerebral infarction. Our results might provide a new strategy and target for the prevention and treatment of PSH.

Diet-derived circulating antioxidants and risk of epilepsy: A study combining metabolomics and mendelian randomization.

Background: Previous studies offer inconclusive results on the association between diet-derived circulating antioxidants and epilepsy. Objective: This study aims to assess oxidative stress presence in epilepsy patients' circulation and investigate the causal link between diet-derived circulating antioxidants and epilepsy. Methods: Untargeted metabolomics analysis was conducted on plasma samples from 62 epileptic patients and 20 healthy individuals to evaluate oxidative stress based on metabolite alterations in epilepsy patients' circulation. Two-sample Mendelian Randomization (MR) analysis examined the causation between diet-derived circulating antioxidants (measured by absolute levels and relative metabolite concentrations) and epilepsy, utilizing the inverse-variance weighted (IVW) method as the primary outcome, with complementary MR analysis methods (MR Egger, weighted median, weighted mode, and simple mode). Results: Untargeted metabolomics analysis revealed elevated circulating oxidizing metabolites (palmitic acid, oleic acid, linoleic acid, and myristic acid) and reduced reducing metabolites (glutamine) in epilepsy patients, providing robust evidence of oxidative stress. The IVW analysis indicated significantly reduced epilepsy risk (odds ratio: 0.552; 95% confidence interval: 0.335-0.905, P = 0.018) with genetically determined higher absolute circulating ß-carotene. However, other diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, and selenium) and antioxidant metabolites (α-tocopherol, γ-tocopherol, ascorbic acid, and retinol) did not significantly associate with epilepsy risk. Additional MR analysis methods and heterogeneity assessments confirmed the results' robustness. Conclusion: This study provides compelling evidence of oxidative stress in epilepsy patients' circulation. However, the majority of diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, vitamin E, and selenium) are unlikely to causally associate with reduced epilepsy risk, except for ß-carotene.

Metabolic signatures and potential biomarkers of sarcopenia in suburb-dwelling older Chinese: based on untargeted GC-MS and LC-MS.

BACKGROUND: Untargeted metabolomics can be used to expand our understanding of the pathogenesis of sarcopenia. However, the metabolic signatures of sarcopenia patients have not been thoroughly investigated. Herein, we explored metabolites associated with sarcopenia by untargeted gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) and identified possible diagnostic markers. METHODS: Forty-eight elderly subjects with sarcopenia were age and sex matched with 48 elderly subjects without sarcopenia. We first used untargeted GC/LC-MS to analyze the plasma of these participants and then combined it with a large number of multivariate statistical analyses to analyze the data. Finally, based on a multidimensional analysis of the metabolites, the most critical metabolites were considered to be biomarkers of sarcopenia. RESULTS: According to variable importance in the project (VIP > 1) and the p-value of t-test (p < 0.05), a total of 55 metabolites by GC-MS and 85 metabolites by LC-MS were identified between sarcopenia subjects and normal controls, and these were mostly lipids and lipid-like molecules. Among the top 20 metabolites, seven phosphatidylcholines, seven lysophosphatidylcholines (LysoPCs), phosphatidylinositol, sphingomyelin, palmitamide, L-2-amino-3-oxobutanoic acid, and palmitic acid were downregulated in the sarcopenia group; only ethylamine was upregulated. Among that, three metabolites of LysoPC(17:0), L-2-amino-3-oxobutanoic acid, and palmitic acid showed very good prediction capacity with AUCs of 0.887 (95% CI = 0.817-0.957), 0.836 (95% CI = 0.751-0.921), and 0.805 (95% CI = 0.717-0.893), respectively. CONCLUSIONS: These findings show that metabonomic analysis has great potential to be applied to sarcopenia. The identified metabolites could be potential biomarkers and could be used to study sarcopenia pathomechanisms.

Association of the combination of obstructive sleep apnea risk and sleep duration with ideal cardiovascular health metrics in patients undergoing hemodialysis.

BACKGROUND: The purpose of this study was to explore the separate and combined associations of obstructive sleep apnea (OSA) risk and sleep duration with ideal cardiovascular health metrics in hemodialysis (HD) patients. METHODS: 470 HD participants (average: 59.48 ± 12.89 y, 281 men) were included in this study. Sleep duration was measured as self-reported average sleep time during the previous month. The OSA risk was assessed using the STOP-BANG questionnaire. Participants were divided into three groups based on the number of ideal cardiovascular health (CVH) metrics: 0-2,3-4, and 5-7. Ordinal logistic regression was conducted to model the associations of CVH metrics with sleep duration, OSA risk, and their combined effects by adjusting for specific covariates. RESULTS: After adjusting for covariates, short sleep duration (< 7 h) (OR = 0.53; 95% CI [ 0.30, 0.92]) and OSA risk (OR = 0.58; 95% CI [0.32, 0.83]) were negatively associated with better CVH (ideal vs. intermediate; intermediate vs. poor), respectively. For HD patients with both short sleep duration and OSA risk, the odds of ideal CVH metrics were reduced by 72% (odds ratio 0.28 [95% CI 0.13, 0.60]). CONCLUSIONS: Short sleep duration and OSA risk are separately and jointly associated with poor CVH in hemodialysis patients. Suitable interventions for sleep may minimize the risk of developing cardiovascular disease.

Comparative Analysis of Plant Growth-Promoting Rhizobacteria's Effects on Alfalfa Growth at the Seedling and Flowering Stages under Salt Stress.

Alfalfa (Medicago sativa L.), a forage legume known for its moderate salt-alkali tolerance, offers notable economic and ecological benefits and aids in soil amelioration when cultivated in saline-alkaline soils. Nonetheless, the limited stress resistance of alfalfa could curtail its productivity. This study investigated the salt tolerance and growth-promoting characteristics (in vitro) of four strains of plant growth-promoting rhizobacteria (PGPR) that were pre-selected, as well as their effects on alfalfa at different growth stages (a pot experiment). The results showed that the selected strains belonged to the genera Priestia (HL3), Bacillus (HL6 and HG12), and Paenibacillus (HG24). All four strains exhibited the ability to solubilize phosphate and produce indole-3-acetic acid (IAA) and 1-aminocyclopropane-1-carboxylate (ACC) deaminase. Among them, except for strain HG24, the other strains could tolerate 9% NaCl stress. Treatment with 100 mM NaCl consistently decreased the IAA production levels of the selected strains, but inconsistent changes (either enhanced or reduced) in terms of phosphate solubilization, ACC deaminase, and exopolysaccharides (EPS) production were observed among the strains. During the various growth stages of alfalfa, PGPR exhibited different growth-promoting effects: at the seedling stage, they enhanced salt tolerance through the induction of physiological changes; at the flowering stage, they promoted growth through nutrient acquisition. The current findings suggest that strains HL3, HL6, and HG12 are effective microbial inoculants for alleviating salt stress in alfalfa plants in arid and semi-arid regions. This study not only reveals the potential of indigenous salt-tolerant PGPR in enhancing the salt tolerance of alfalfa but also provides new insights into the mechanisms of action of PGPR.