Statin use and development and progression of non-alcohol fatty liver disease based on ultrasonography: a cohort study.

INTRODUCTION: Non-alcohol fatty liver disease (NAFLD) has emerged as a public health issue, while no drugs have been specifically approved for treatment. This study aimed to examine the association between statin use and NAFLD occurrence, progression, and regression. METHODS: A cohort study was designed based on the Kailuan Study and electronic medical records (EMRs) from the Kailuan General Hospital. Participants aged 18 years with statin indication, including statin and non-statin users, were enrolled in 2010-2017. Propensity score-matched cohorts were also used. RESULTS: In the entire cohort, 21 229 non-NAFLD and 22 419 NAFLD patients (including 12 818 mild NAFLD) were included in the final analysis. After a median follow-up of about four years, the incidence of NAFLD occurrence and progression for statin users were lower than those for non-statin users (occurrence: 84.7 vs. 106.5/1000 person-years; progression: 60.7 vs. 75.5/1000 person-years). Compared with non-statin users, the risk of NAFLD occurrence (hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.70-0.87) and regression (HR [95%CI], 0.71[0.60-0.84]) was decreased in statin users. The significantly negative association was only observed in those with cumulative statin duration ≥ 2 years (HR [95%CI] for occurrence 0.56 [0.46-0.69] vs. 0.52 [0.30-0.90] for progression) and those with low or moderate ASCVD-risk (HR [95%CI] for occurrence 0.74 [0.66-0.82] vs. 0.68 [0.57-0.80] for progression). No significant correlation was observed between statin use, statin use duration, and NAFLD regression. The PS-matched cohort had similar results. CONCLUSION: Taking statin may decrease the risk of NAFLD occurrence and progression in the population with statin indication, suggesting the potential role of statin in both primary and secondary prevention strategies for NAFLD, especially among those with low or moderate ASCVD risk.

Gender and age related brain structural and functional alterations in children with autism spectrum disorder.

To explore the effects of age and gender on the brain in children with autism spectrum disorder using magnetic resonance imaging. 185 patients with autism spectrum disorder and 110 typically developing children were enrolled. In terms of gender, boys with autism spectrum disorder had increased gray matter volumes in the insula and superior frontal gyrus and decreased gray matter volumes in the inferior frontal gyrus and thalamus. The brain regions with functional alterations are mainly distributed in the cerebellum, anterior cingulate gyrus, postcentral gyrus, and putamen. Girls with autism spectrum disorder only had increased gray matter volumes in the right cuneus and showed higher amplitude of low-frequency fluctuation in the paracentral lobule, higher regional homogeneity and degree centrality in the calcarine fissure, and greater right frontoparietal network-default mode network connectivity. In terms of age, preschool-aged children with autism spectrum disorder exhibited hypo-connectivity between and within auditory network, somatomotor network, and visual network. School-aged children with autism spectrum disorder showed increased gray matter volumes in the rectus gyrus, superior temporal gyrus, insula, and suboccipital gyrus, as well as increased amplitude of low-frequency fluctuation and regional homogeneity in the calcarine fissure and precentral gyrus and decreased in the cerebellum and anterior cingulate gyrus. The hyper-connectivity between somatomotor network and left frontoparietal network and within visual network was found. It is essential to consider the impact of age and gender on the neurophysiological alterations in autism spectrum disorder children when analyzing changes in brain structure and function.

Phosphoribosylpyrophosphate synthetase as a metabolic valve advances Methylobacterium/Methylorubrum phyllosphere colonization and plant growth.

The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.

Structure-guided isolation of anti-neuroinflammatory sesquiterpene coumarins from Ferula sinkiangensis.

The resin of Ferula sinkiangensis has been traditionally utilized for treating gastrointestinal disorders, inflammation, tumors, various cancers, and alopecia areata. The primary bioactive constituents, sesquiterpene coumarins, have demonstrated notable therapeutic potential against neuroinflammation. In this study, a structure-guided fractionation method was used to isolate nine novel sesquiterpene coumarins from the resin of F. sinkiangensis. These compounds were characterized and structurally elucidated using comprehensive physicochemical and spectroscopic techniques, including calculated electronic circular dichroism (ECD). Anti-neuroinflammatory assays revealed that compounds 2, 3, and 6 significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, with IC50 values ranging from 1.63 to 12.25 µmol·L-1.

2, 9-deoxyflavonoids (= 3-aryl-1-indanones) from Aglaia odorata: Structure elucidation, biosynthetic pathway and lung protective activity.

Six previously undescribed 2, 9-deoxyflavonoids (1/2a, 1/2b, 6, and 7), along with six known compounds (3-5, and 8-10), were isolated from the twigs and leaves of Aglaia odorata. Their structures were determined by a combination of spectral analysis, ECD calculation and enzymatic hydrolysis assay. Surprisingly, (±) aglaindanone E (11a, 11b) were unexpectedly formed as the derivatives of compounds 3-6 when exposed to ambient natural light. Furthermore, the plausible biosynthetic pathway of 2, 9-deoxyflavonoids was proposed and chemically mimicked. In biological activity assay, compounds 1/2a, 1/2b, 4, and 6 showed potential protective effects in the 0.75%CSE-induced BEAS-2B cells injury model.

Clinical Analysis of Different Anesthesia and Analgesia Methods for Patients Undergoing Uniportal Video-assisted Lung Surgery.

PURPOSE: The purpose of this study was to compare 3 intraoperative modalities to determine the best and most convenient one for pain control for uniportal lung surgery. This study compared general anesthesia with serratus plane block, general anesthesia with epidural, and general anesthesia alone to examine postoperative pain scores in patients. METHODS: Eighty patients were enrolled and statistically analyzed. Three interventions were studied: general anesthesia with serratus plane block (group S), general anesthesia with thoracic epidural (group E), and general anesthesia only (group G). Outcome measures compared among the 3 groups included demographic characteristics; surgical types; anesthesia and operative time; postoperative pain scores; vital signs; morphine consumption at 0, 2, and 6 hours and day 1 and day 2 after surgery; incidence of opioid-related adverse events and chronic pain; hospital length of stay (LOS); and overall expenses. The numerical rating scale was used to assess the degree of pain on the first and second postoperative days. Postoperative morphine consumption, incidence of opioid-related side effects, hospital LOS, and overall hospital expenses were documented, as well as incidence of chronic postoperative pain. FINDINGS: There was no difference in the incidence of opioid-related adverse events and chronic pain, hospital LOS, and overall expenses among the 3 groups. After investigating factors that may influence hospital LOS and overall expenses, the multivariable analysis indicated that only longer operative time was associated with longer hospital stay and more hospital expenses. IMPLICATIONS: This prospective study found that general anesthesia alone offers an easy and efficient approach resulting in similar postoperative pain scores and morphine consumption compared with nerve block and epidural. Longer operative time was associated with longer hospital stay and more hospital expenses. CLINICALTRIALS: gov identifier: NCT03839160. (Clin Ther. 2024;XX:XXX-XXX) © 2024 Elsevier HS Journals, Inc.

Differential processing of RNA polymerase II at DNA damage correlates with transcription-coupled repair syndrome severity.

DNA damage severely impedes gene transcription by RNA polymerase II (Pol II), causing cellular dysfunction. Transcription-Coupled Nucleotide Excision Repair (TC-NER) specifically removes such transcription-blocking damage. TC-NER initiation relies on the CSB, CSA and UVSSA proteins; loss of any results in complete TC-NER deficiency. Strikingly, UVSSA deficiency results in UV-Sensitive Syndrome (UVSS), with mild cutaneous symptoms, while loss of CSA or CSB activity results in the severe Cockayne Syndrome (CS), characterized by neurodegeneration and premature aging. Thus far the underlying mechanism for these contrasting phenotypes remains unclear. Live-cell imaging approaches reveal that in TC-NER proficient cells, lesion-stalled Pol II is swiftly resolved, while in CSA and CSB knockout (KO) cells, elongating Pol II remains damage-bound, likely obstructing other DNA transacting processes and shielding the damage from alternative repair pathways. In contrast, in UVSSA KO cells, Pol II is cleared from the damage via VCP-mediated proteasomal degradation which is fully dependent on the CRL4CSA ubiquitin ligase activity. This Pol II degradation might provide access for alternative repair mechanisms, such as GG-NER, to remove the damage. Collectively, our data indicate that the inability to clear lesion-stalled Pol II from the chromatin, rather than TC-NER deficiency, causes the severe phenotypes observed in CS.

Weiwei Decoction alleviates gastric intestinal metaplasia through the olfactomedin 4/nucleotide-binding oligomerization domain 1/caudal-type homeobox gene 2 signaling pathway.

BACKGROUND: Gastric intestinal metaplasia (IM) is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis. Weiwei Decoction (WWD) is a promising traditional Chinese herbal formula widely employed in clinical for treating IM. Previous studies suggested the potential involvement of the olfactomedin 4 (OLFM4)/nucleotide-binding oligomerization domain 1 (NOD1)/caudal-type homeobox gene 2 (CDX2) signaling pathway in IM regulation. AIM: To verify the regulation of the OLFM4/NOD1/CDX2 pathway in IM, specifically investigating WWD's effectiveness on IM through this pathway. METHODS: Immunohistochemistry for OLFM4, NOD1, and CDX2 was conducted on tissue microarray. GES-1 cells treated with chenodeoxycholic acid were utilized as IM cell models. OLFM4 short hairpin RNA (shRNA), NOD1 shRNA, and OLFM4 pcDNA were transfected to clarify the pathway regulatory relationships. Protein interactions were validated by co-immunoprecipitation. To explore WWD's pharmacological actions, IM rat models were induced using N-methyl-N'-nitro-N-nitrosoguanidine followed by WWD gavage. Gastric cells were treated with WWD-medicated serum. Cytokines and chemokines content were assessed by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. RESULTS: The OLFM4/NOD1/CDX2 axis was a characteristic of IM. OLFM4 exhibited direct binding and subsequent down-regulation of NOD1, thereby sustaining the activation of CDX2 and promoting the progression of IM. WWD improved gastric mucosal histological lesions while suppressing intestinal markers KLF transcription factor 4, villin 1, and MUCIN 2 expression in IM rats. Regarding pharmacological actions, WWD suppressed OLFM4 and restored NOD1 expression, consequently reducing CDX2 at the mRNA and protein levels in IM rats. Parallel regulatory mechanisms were observed at the protein level in IM cells treated with WWD-medicated serum. Furthermore, WWD-medicated serum treatment strengthened OLFM4 and NOD1 interaction. In case of anti-inflammatory, WWD restrained interleukin (IL)-6, interferon-gamma, IL-17, macrophage chemoattractant protein-1, macrophage inflammatory protein 1 alpha content in IM rat serum. WWD-medicated serum inhibited tumor necrosis factor alpha, IL-6, IL-8 transcriptions in IM cells. CONCLUSION: The OLFM4/NOD1/CDX2 pathway is involved in the regulation of IM. WWD exerts its therapeutic efficacy on IM through the pathway, additionally attenuating the inflammatory response.

Efficacy and safety of upadacitinib in the treatment of moderate-to-severe atopic dermatitis: A systematic review.

OBJECTIVE: To evaluate the efficacy and safety of upadacitinib in the treatment of moderate-to-severe atopic dermatitis (AD), and provide reference for rational clinical medication. METHODS: PubMed, Medline, Embase, Web of Science, Clinical Trials Website, and Cochrane Library databases were searched from the time of establishment until January 6, 2024, to compile a list of all randomized controlled trials (RCTs) including upadacitinib in the treatment of moderate-to-severe AD. The quality of the included studies was evaluated using the Cochrane Systematic Review. Review Manager 5.3 software was utilized for statistical analysis of outcome measures. RESULTS: A total of five studies were included in the meta-analysis. The results revealed that the 15 mg and 30 mg upadacitinib significantly improved Eczema Area and Severity Index (EASI) 75% {[Odds Ratio (OR) = 8.58, 95% confidence interval (CI) (5.84-12.60), P < 0.00001] [OR = 15.62, 95% CI (10.89-22.42), P < 0.00001]}, Numerical Rating Scale (NRS) ≥ 4 {[OR = 7.13, 95% CI (5.63-9.01), P < 0.00001] [OR = 11.30, 95% CI (8.93-14.31), P < 0.00001]}, and Investigator's Global Assessment (IGA) 0/1 {[OR = 8.63, 95% CI (6.60-11.27), P < 0.00001] [OR = 16.04, 95% CI (12.26-20.99), P < 0.00001]} compared to placebo. In terms of safety, although 15 mg and 30 mg upadacitinib significantly increased the overall adverse events rate compared to placebo {[OR = 1.31, 95% CI (1.09-1.58), P = 0.004] [OR = 1.85, 95% CI (1.54-2.21), P < 0.00001]}, there was no significant difference in the serious adverse events rate {[OR = 0.73, 95% CI (0.41-1.29), P = 0.28] [OR = 0.69, 95% CI (0.39-1.23), P = 0.21]} and withdrawal rate due to adverse events {[OR = 0.66, 95% CI (0.39-1.11), P = 0.12] [OR = 0.85, 95% CI (0.52-1.38), P = 0.50]} compared to placebo. CONCLUSION: This meta-analysis preliminarily suggests that upadacitinib is effective and safe for usage in the treatment of moderate-to-severe AD. Additionally, upadacitinib can instantly relieve itchiness and effectively reduce symptoms and signs, with its 30-mg dose being more effective than the 15-mg dose.

Programmable photoacoustic manipulation of microparticles in liquid.

Particle manipulation through the transfer of light or sound momentum has emerged as a powerful technique with immense potential in various fields, including cell biology, microparticle assembly, and lab-on-chip technology. Here, we present a novel method called Programmable Photoacoustic Manipulation (PPAM) of microparticles in liquid, which enables rapid and precise arrangement and controllable transport of numerous silica particles in water. Our approach leverages the modulation of pulsed laser using digital micromirror devices (DMD) to generate localized Lamb waves in a stainless steel membrane and acoustic waves in water. The particles undergo a mechanical force of about several µN due to membrane vibrations and an acoustic radiation force of about tens of nN from the surrounding water. Consequently, this approach surpasses the efficiency of optical tweezers by effectively countering the viscous drag imposed by water and can be used to move thousands of particles on the membrane. The high power of the pulsed laser and the programmability of the DMD enhance the flexibility in particle manipulation. By integrating the benefits of optical and acoustic manipulation, this technique holds great promise for advancing large-scale manipulation, cell assembly, and drug delivery.

Reynosin protects neuronal cells from microglial neuroinflammation by suppressing NLRP3 inflammasome activation mediated by NADPH oxidase.

Neuroinflammation, mediated by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome, is a significant contributor to the pathogenesis of neurodegenerative diseases (NDDs). Reynosin, a natural sesquiterpene lactone (SL), exhibits a broad spectrum of pharmacological effects, suggesting its potential therapeutic value. However, the effects and mechanism of reynosin on neuroinflammation remain elusive. The current study explores the effects and mechanisms of reynosin on neuroinflammation using mice and BV-2 microglial cells treated with lipopolysaccharide (LPS). Our findings reveal that reynosin effectively reduces microglial inflammation in vitro, as demonstrated by decreased CD11b expression and lowered interleukin-1 beta (IL-1ß) and interleukin-18 (IL-18) mRNA and protein levels. Correspondingly, in vivo, results showed a reduction in the number of Iba-1 positive cells and alleviation of morphological alterations, alongside decreased expressions of IL-1ß and IL-18. Further analysis indicates that reynosin inhibits NLRP3 inflammasome activation, evidenced by reduced transcription of NLRP3 and caspase-1, diminished NLRP3 protein expression, inhibited apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, and decreased caspase-1 self-cleavage. Additionally, reynosin curtailed the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, demonstrated by reduced NADP+ and NADPH levels, downregulation of gp91phox mRNA, protein expression, suppression of p47phox expression and translocation to the membrane. Moreover, reynosin exhibited a neuroprotective effect against microglial inflammation in vivo and in vitro. These collective findings underscore reynosin's capacity to mitigate microglial inflammation by inhibiting the NLRP3 inflammasome, thus highlighting its potential as a therapeutic agent for managing neuroinflammation.

Treg and neutrophil extracellular trap interaction contributes to the development of immunosuppression in sepsis.

The excessive formation and release of neutrophil extracellular traps (NETs) in sepsis may represent a substantial mechanism contributing to multiorgan damage, which is associated with a poor prognosis. However, the precise role of NETs in mediating the transition from innate immunity to adaptive immunity during the progression of inflammation and sepsis remains incompletely elucidated. In this study, we provide evidence that, despite a reduction in the number of CD4+ T cells in the late stage of sepsis, there is a notable upregulation in the proportion of Tregs. Mechanistically, we have identified that NETs can induce metabolic reprogramming of naive CD4+ T cells through the Akt/mTOR/SREBP2 pathway, resulting in enhanced cholesterol metabolism, thereby promoting their conversion into Tregs and augmenting their functional capacity. Collectively, our findings highlight the potential therapeutic strategy of targeting intracellular cholesterol normalization for the management of immunosuppressed patients with sepsis.

Microcin Y utilizes its stable structure and biological activity to regulate the metabolism of intestinal probiotics and effectively clear gut Salmonella.

MccY is a novel, structurally stable microcin with antibacterial activity against Enterobacteriaceae. However, the bioavailability of orally administrated MccY is unknown. This study evaluated the effects of MccY as a antimicrobial on pre-digestion in vitro and its intake, digestion and gut metabolism in vivo. The result of pre-digestion results that MccY maintained its biological activity and was resistant to decomposition. The study established a safe threshold of 4.46-9.92 mg/kg for the MccY dosage-body weight relationship in BALB/c mice. Mice fed with MccY demonstrated improved body weight and intestinal barrier function, accompanied with increased IgM immunogenicity and decreased levels of TNF-α, IL-6, and IL-10 in the intestine. MccY significantly facilitates the growth and activity of probiotics including Lactobacillus, Prevotella, and Bacteroides, and leading to the production of SCFAs and MCFAs during bacterial interactions. Furthermore, MccY effectively protects against the inflammatory response caused by Salmonella Typhimurium infection and effectively clears the Salmonella bacteria from the gut. In conclusion, MccY is seen as a promising new therapeutic target drug for enhancing the intestinal microbe-barrier axis and preventing enteritis.

Schisandrin B inhibits inflammation and ferroptosis in S.aureus-induced mastitis through regulating SIRT1/p53/SLC7A11 signaling pathway.

Mastitis, one of the most significant problems in women, is commonly caused by pathogens, especially Staphylococcus aureus (S.aureus). Schisandrin B (SCB), the main abundant derivatives from Schisandra chinensis, has been proven to have the ability to inhibiting inflammation and bacteria. However, few relevant researches systematically illustrate the role SCB in the treatment of mastitis. The aim of the present study is to demonstrate the mechanism that SCB functions in reducing pathological injury to the mammary gland in treating S.aureus-induced mastitis. H&E staining was used to identify pathological changes and injuries in mastitis. The levels of cytokines associated with inflammation were detected by ELISA. Key signals relevant to ferroptosis and Nrf2 signaling pathway were tested by western blot analysis and iron assay kit. Compared with the control group, inflammation-associated factors, such as IL-1ß, TNF-α, MPO activity, increased significantly in S. aureus-treated mice. However, these changes were inhibited by SCB. Ferroptosis-associated factors Fe2+ and MDA increased significantly, and GSH, GPX4 and ferritin expression decreased markedly in S. aureus-treated mice. SCB treatment could attenuate S.aureus-induced ferroptosis. Furthermore, SCB increase SIRT1 and SLC7A11 expression and down-regulated p53 expression and NF-κB activation. In conclusion, SCB alleviates S.aureus-induced mastitis via up-regulating SIRT1/p53/SLC7A11 signaling pathway, attenuating the activation of inflammation-associated cytokines and ferroptosis in the mammary gland tissues.

Axially chiral dihydrophenanthrene dimers from Pholidota yunnanensis with anti-neuroinflammatory activities.

Axially chiral compounds are well known in medicinal chemistry of natural products, but their absolute configurations and bioactivities are rarely reported and studied. In this study, eleven undescribed axially chiral dihydrophenanthrene dimers, as well as twenty-five known dihydrophenanthrenes, were isolated from the entire plant of Pholidota yunnanensis. Their structures were elucidated by comprehensive spectroscopic analysis. A method for determining the absolute configurations of enantiomers was developed based on the rotational barriers and calculated ECD spectra. Additionally, the activities of all isolated compounds were assessed in LPS-induced BV-2 microglial cells. Most dihydrophenanthrenes exhibited significant NO inhibitory activities, and compound 7 showed the most potent inhibitory effect with an IC50 value of 1.5 µM, compared to the positive control minocycline. The immunofluorescence and western blot results revealed that compound 7 suppressed the expression of Iba-1, iNOS and COX-2 in LPS-stimulated BV-2 microglial cells.

A Bacillus velezensis strain isolated from oats with disease-preventing and growth-promoting properties.

Endophytes have been shown to promote plant growth and health. In the present study, a Bacillus velezensis CH1 (CH1) strain was isolated and identified from high-quality oats, which was capable of producing indole-3-acetic acid (IAA) and strong biofilms, and capabilities in the nitrogen-fixing and iron carriers. CH1 has a 3920 kb chromosome with 47.3% GC content and 3776 code genes. Compared genome analysis showed that the largest proportion of the COG database was metabolism-related (44.79%), and 1135 out of 1508 genes were associated with the function "biosynthesis, transport, and catabolism of secondary metabolites." Furthermore, thirteen gene clusters had been identified in CH1, which were responsible for the synthesis of fifteen secondary metabolites that exhibit antifungal and antibacterial properties. Additionally, the strain harbors genes involved in plant growth promotion, such as seven putative genes for IAA production, spermidine and polyamine synthase genes, along with multiple membrane-associated genes. The enrichment of these functions was strong evidence of the antimicrobial properties of strain CH1, which has the potential to be a biofertilizer for promoting oat growth and disease resistance.

Heart Failure with Normal Natriuretic Peptide Levels and Preserved Ejection Fraction: A Prospective Clinical and Cardiac MRI Study.

Purpose To describe the clinical presentation, comprehensive cardiac MRI characteristics, and prognosis of individuals with predisposed heart failure with preserved ejection fraction (HFpEF). Materials and Methods This prospective cohort study (part of MISSION-HFpEF [Multimodality Imaging in the Screening, Diagnosis, and Risk Stratification of HFpEF]; NCT04603404) was conducted from January 1, 2019, to September 30, 2021, and included individuals with suspected HFpEF who underwent cardiac MRI. Participants who had primary cardiomyopathy and primary valvular heart disease were excluded. Participants were split into a predisposed HFpEF group, defined as HFpEF with normal natriuretic peptide levels based on an HFA-PEFF (Heart Failure Association Pretest Assessment, Echocardiography and Natriuretic Peptide, Functional Testing, and Final Etiology) score of 4 from the latest European Society of Cardiology guidelines, and an HFpEF group (HFA-PEFF score of ≥ 5). An asymptomatic control group without heart failure was also included. Clinical and cardiac MRI-based characteristics and outcomes were compared between groups. The primary end points were death, heart failure hospitalization, or stroke. Results A total of 213 participants with HFpEF, 151 participants with predisposed HFpEF, and 100 participants in the control group were analyzed. Compared with the control group, participants with predisposed HFpEF had worse left ventricular remodeling and function and higher systemic inflammation. Compared with participants with HFpEF, those with predisposed HFpEF, whether obese or not, were younger and had higher plasma volume, lower prevalence of atrial fibrillation, lower left atrial volume index, and less impaired left ventricular global longitudinal strain (-12.2% ± 2.8 vs -13.9% ± 3.1; P < .001) and early-diastolic global longitudinal strain rate (eGLSR, 0.52/sec ± 0.20 vs 0.57/sec ± 0.15; P = .03) but similar prognosis. Atrial fibrillation occurrence (hazard ratio [HR] = 3.90; P = .009), hemoglobin level (HR = 0.94; P = .001), and eGLSR (per 0.2-per-second increase, HR = 0.28; P = .002) were independently associated with occurrence of primary end points in participants with predisposed HFpEF. Conclusion Participants with predisposed HFpEF showed relatively unique clinical and cardiac MRI features, warranting greater clinical attention. eGLSR should be considered as a prognostic factor in participants with predisposed HFpEF. Keywords: Heart Failure with Preserved Ejection Fraction, Normal Natriuretic Peptide Levels, Cardiovascular Magnetic Resonance, Myocardial Strain, Prognosis Clinical trial registration no. NCT04603404 Supplemental material is available for this article. © RSNA, 2024.

Characteristic terpenylated coumarins from Ferula ferulaeoides as potential inhibitors on overactivation of microglia.

A total of 37 characteristic terpenylated coumarins (1-25), including 17 undescribed compounds (1-5, 6a/6b, 7-10, 11a/11b-13a/13b), have been isolated from the root of Ferula ferulaeoides. Meanwhile, twelve pairs of enantiomers (6a/6b, 11a/11b-15a/15b, 17a/17b, 18a/18b, 20a/20b-22a/22b, and 25a/25b) were chirally purified. The structures of these new compounds were elucidated using HRESIMS, UV, NMR, and calculated 13C NMR with a custom DP4 + analysis. The absolute configurations of all the compounds were determined for the first time using electronic circular dichroism (ECD). Then, their inhibitory effects on nitric oxide (NO) production were evaluated with LPS-induced BV-2 microglia. Compared with the positive control minocycline (IC50 = 59.3 µM), ferulaferone B (2) exhibited stronger inhibitory potency with an IC50 value of 12.4 µM. The immunofluorescence investigation indicated that ferulaferone B (2) could inhibit Iba-1 expression in LPS-stimulated BV-2 microglia.

Effect of oral administration of microcin Y on growth performance, intestinal barrier function and gut microbiota of chicks challenged with Salmonella Pullorum.

The lasso peptide microcin Y (MccY) effectively inhibits various serotypes of Salmonella in vitro, but the antibacterial effect against S. Pullorum in poultry is still unclear. This study was the first to evaluate the safety and anti-S. Pullorum infection of MccY in specific pathogen-free (SPF) chicks. The safety test showed that the body weight, IgA and IgM levels of serum, and cecal microbiota structure of 3 groups of chicks orally administrated with different doses of MccY (5 mg/kg, 10 mg/kg, 20 mg/kg) for 14 days were not significantly different from those of the control group. Then, the chicks were randomized into 3 groups for the experiment of anti-S. Pullorum infection: (I) negative control group (NC), (II) S. Pullorum-challenged group (SP, 5 × 108 CFU/bird), (III) MccY-treated group (MccY, 20 mg/kg). The results indicated that compared to the SP group, treatment of MccY increased body weight and average daily gain (P < 0.05), reduced S. Pullorum burden in feces, liver, and cecum (P < 0.05), enhanced the thymus, and decreased the spleen and liver index (P < 0.05). Additionally, MccY increased the jejunal villus height, lowered the jejunal and ileal crypt depth (P < 0.05), and upregulated the expression of IL-4, IL-10, ZO-1 in the jejunum and ileum, as well as CLDN-1 in the jejunum (P < 0.05) compared to the SP group. Furthermore, MccY increased probiotic flora (Barnesiella, etc.), while decreasing (P < 0.05) the relative abundance of pathogenic flora (Escherichia and Salmonella, etc.) compared to the SP group.

Daphnane diterpenoid orthoesters with an odd-numbered aliphatic side chain from Daphne pedunculata.

Daphnane diterpenoids were recognized for their extensive range of potent biological activities. In the present study, phytochemical investigation including LC-MS/MS analysis resulted in the identification of five daphnane diterpenoid orthoesters (1-5). Among the five daphnane diterpenoids, two previously unreported compounds, daphnepedunins I and J (2 and 4) were isolated from Daphne pedunculata. The structure of new compounds was elucidated with extensive physicochemical and spectroscopic analyses. Their structure was characterized by the presence of an unusual odd-numbered aliphatic chain connected to an orthoester. The isolated compounds were evaluated for their anti-HIV activity against HIV-1 infection of MT4 cells, and the results indicated that compound 1 showed the most potent anti-HIV activity with an IC50 value of 0.82 nM.