Mitochondrial-targeted cyclometalated Ir(III)-5,7-dibromo/dichloro-2-methyl-8-hydroxyquinoline complexes and their anticancer efficacy evaluation in Hep-G2 cells.

Both 8-hydroxyquinoline compounds and iridium (Ir) complexes have emerged as potential novel agents for tumor therapy. In this study, we synthesized and characterized two new Ir(III) complexes, [Ir(L1)(bppy)2] (Br-Ir) and [Ir(L2)(bppy)2] (Cl-Ir), with 5,7-dibromo-2-methyl-8-hydroxyquinoline (HL-1) or 5,7-dichloro-2-methyl-8-hydroxyquinoline (HL-2) as the primary ligand. Complexes Br-Ir and Cl-Ir successfully inhibited antitumor activity in Hep-G2 cells. In addition, complexes Br-Ir and Cl-Ir were localized in the mitochondrial membrane and caused mitochondrial damage, autophagy, and cellular immunity in Hep-G2 cells. We tested the proteins related to mitochondrial and mitophagy by western blot analysis, which showed that they triggered mitophagy-mediated apoptotic cell death. Remarkably, complex Br-Ir showed high in vivo antitumor activity, and the tumor growth inhibition rate (IR) was 63.0% (p <0.05). In summary, our study on complex Br-Ir revealed promising results in in vitro and in vivo antitumor activity assays.

Impact of repetitive transcranial magnetic stimulation on cortical activity: a systematic review and meta-analysis utilizing functional near-infrared spectroscopy evaluation.

BACKGROUND: Repeated transcranial magnetic stimulation (rTMS) could induce alterations in cortical excitability and promote neuroplasticity. To precisely quantify these effects, functional near-infrared spectroscopy (fNIRS), an optical neuroimaging modality adept at detecting changes in cortical hemodynamic responses, has been employed concurrently alongside rTMS to measure and tailor the impact of diverse rTMS protocols on the brain cortex. OBJECTIVE: This systematic review and meta-analysis aimed to elucidate the effects of rTMS on cortical hemodynamic responses over the primary motor cortex (M1) as detected by fNIRS. METHODS: Original articles that utilized rTMS to stimulate the M1 cortex in combination with fNIRS for the assessment of cortical activity were systematically searched across the PubMed, Embase, and Scopus databases. The search encompassed records from the inception of these databases up until April, 2024. The assessment for risk of bias was also conducted. A meta-analysis was also conducted in studies with extractable raw data. RESULTS: Among 312 studies, 14 articles were eligible for qualitative review. 7 studies were eligible for meta-analysis. A variety of rTMS protocols was employed on M1 cortex. In inhibitory rTMS, multiple studies observed a reduction in the concentration of oxygenated hemoglobin [HbO] at the ipsilateral M1, contrasted by an elevation at the contralateral M1. Meta-analysis also corroborated this consistent trend. Nevertheless, certain investigations unveiled diminished [HbO] in bilateral M1. Several studies also depicted intricate inhibitory or excitatory interplay among distinct cortical regions. CONCLUSION: Diverse rTMS protocols led to varied patterns of cortical activity detected by fNIRS. Meta-analysis revealed a trend of increasing [HbO] in the contralateral cortices and decreasing [HbO] in the ipsilateral cortices following low frequency inhibitory rTMS. However, due to the heterogeneity between studies, further research is necessary to comprehensively understand rTMS-induced alterations in brain activity.

Assessment of subclinical LV myocardial dysfunction in T2DM patients with diabetic peripheral neuropathy: a cardiovascular magnetic resonance study.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, and has been demonstrated to be independently associated with cardiovascular events and mortality. This aim of this study was to investigate the subclinical left ventricular (LV) myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients with and without DPN. METHODS: One hundred and thirty T2DM patients without DPN, 61 patients with DPN and 65 age and sex-matched controls who underwent cardiovascular magnetic resonance (CMR) imaging were included, all subjects had no symptoms of heart failure and LV ejection fraction ≥ 50%. LV myocardial non-infarct late gadolinium enhancement (LGE) was determined. LV global strains, including radial, circumferential and longitudinal peak strain (PS) and peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were evaluated using CMR feature tracking and compared among the three groups. Multivariable linear regression analyses were performed to determine the independent factors of reduced LV global myocardial strains in T2DM patients. RESULTS: The prevalence of non-infarct LGE was higher in patients with DPN than those without DPN (37.7% vs. 19.2%, p = 0.008). The LV radial and longitudinal PS (radial: 36.60 ± 7.24% vs. 33.57 ± 7.30% vs. 30.72 ± 8.68%; longitudinal: - 15.03 ± 2.52% vs. - 13.39 ± 2.48% vs. - 11.89 ± 3.02%), as well as longitudinal PDSR [0.89 (0.76, 1.05) 1/s vs. 0.80 (0.71, 0.93) 1/s vs. 0.77 (0.63, 0.87) 1/s] were decreased significantly from controls through T2DM patients without DPN to patients with DPN (all p < 0.001). LV radial and circumferential PDSR, as well as circumferential PS were reduced in both patient groups (all p < 0.05), but were not different between the two groups (all p > 0.05). Radial and longitudinal PSSR were decreased in patients with DPN (p = 0.006 and 0.003, respectively) but preserved in those without DPN (all p > 0.05). Multivariable linear regression analyses adjusting for confounders demonstrated that DPN was independently associated with LV radial and longitudinal PS (ß = - 3.025 and 1.187, p = 0.014 and 0.003, respectively) and PDSR (ß = 0.283 and - 0.086, p = 0.016 and 0.001, respectively), as well as radial PSSR (ß = - 0.266, p = 0.007). CONCLUSIONS: There was more severe subclinical LV dysfunction in T2DM patients complicated with DPN than those without DPN, suggesting further prospective study with more active intervention in this cohort of patients.

The intraindividual dynamics of university students' motivation and emotions: The role of autonomy-supportive learning climates and learning activities.

BACKGROUND: The motivation and emotions of students are context dependent. There are specific moments when students may find their coursework more or less motivating, resulting in stronger or milder emotional responses. Identifying factors directly controllable by teachers empowers them to effectively address challenging situations characterized by lower motivation and increased negative emotions. AIMS: We aimed to investigate how learning activities and students' perception of teaching practices fostering autonomy relate to competence and value beliefs, and emotions in the context of course participation within higher education. SAMPLE: Seventy-seven Taiwanese university students provided 762 learning reports associated with their course participation experiences. METHODS: The experience sampling method (ESM) was used. Participants responded to ESM surveys on their phones for 14 days, reporting motivational beliefs, emotions and contextual characteristics of the course if they indicated active participation in a course upon receiving notifications from their phones. RESULTS: A significant portion of the variation is attributed to situational fluctuation, suggesting that academic emotions and competence and value beliefs vary within students across measurements. An increase in students' perception of an autonomy-supportive learning climate correlates with higher competence beliefs, intrinsic value and positive emotions, coupled with reduced perceived costs and negative emotions. In contrast to lectures, engaging in independent hands-on work, participating in group collaborative projects or interactive discussions appear to inspire motivation or evoke stronger emotional responses in students. CONCLUSIONS: Teachers' teaching practices and classroom learning activities play a pivotal role in shaping students' situational motivation and emotions.

Screening for frequently detected quaternary ammonium mixture systems in waters based on frequent itemset mining and prediction of their toxicity.

Screening and prioritizing research on frequently detected mixture systems in the environment is of great significance, as conducting toxicity testing on all mixtures is impractical. Therefore, the frequent itemset mining (FIM) was introduced and applied in this paper to identify variables that commonly co-occur in a dataset. Based on the dataset of the quaternary ammonium compounds (QACs) in the water environment, the four frequent QAC mixture systems with detection rate ≥ 35 % were found, including [BDMM]+Cl--[BTMM]+Cl- (M1), [BDMM]+Cl--[BHMM]+Cl- (M2), [BTMM]+Cl- -[BHMM]+Cl- (M3), and [BDMM]+Cl--[BTMM]+Cl--[BHMM]+Cl- (M4). [BDMM]+Cl-, [BTMM]+Cl-, and [BHMM]+Cl- are benzyl dodecyl dimethyl ammonium chloride, benzyl tetradecyl dimethyl ammonium chloride, and benzyl hexadecyl dimethyl ammonium chloride, respectively. Then, the toxicity of the representative mixture rays and components for the four frequently detected mixture systems was tested using Vibrio qinghaiensis sp.-Q67 (Q67) as a luminescent indicator organism at 0.25 and 12 h. The toxicity of the mixtures was predicted using concentration addition (CA) and independent action (IA) models. It was shown that both the components and the representative mixture rays for the four frequently detected mixture systems exhibited obvious acute and chronic toxicity to Q67, and their median effective concentrations (EC50) were below 7 mg/L. Both CA and IA models predicted the toxicity of the four mixture systems well. However, the CA model had a better predictive ability for the toxicity of the M3 and M4 mixtures than IA at 12 h.

Impact of Functional Mitral Regurgitation on Left Ventricular Strain in Nonischemic Dilated Cardiomyopathy Patients with Type 2 Mellitus Diabetes: A Magnetic Resonance Feature Tracking Study.

BACKGROUND: The impact of functional mitral regurgitation and type 2 mellitus diabetes (T2DM) on left ventricular (LV) strain in nonischemic dilated cardiomyopathy (NIDCM) patients remains unclear. PURPOSE: To evaluate the impact of mitral regurgitation severity on LV strain, and explore additive effect of T2DM on LV function across varying mitral regurgitation severity levels in NIDCM patients. STUDY TYPE: Retrospective. POPULATION: 352 NIDCM (T2DM-) patients (49.1 ± 14.6 years, 67% male) (207, 85, and 60 no/mild, moderate, and severe mitral regurgitation) and 96 NIDCM (T2DM+) patients (55.2 ± 12.4 years, 77% male) (47, 30, and 19 no/mild, moderate, and severe mitral regurgitation). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence. ASSESSMENT: LV geometric parameters and strain were measured and compared among groups. Determinants of LV strain were investigated. STATISTICAL TEST: Student's t-test, Mann-Whitney U test, one-way ANOVA, Kruskal-Wallis test, univariable and multivariable linear regression. P < 0.05 was considered statistically significant. RESULTS: LV GLPS and longitudinal PDSR decreased gradually with increasing mitral regurgitation severity in NIDCM patients with T2DM(GLPS: -5.7% ± 2.1% vs. -4.3% ± 1.6% vs. -2.6% ± 1.3%; longitudinal PDSR:0.5 ± 0.2 sec-1 vs. 0.4 ± 0.2 sec-1 vs. 0.3 ± 0.1 sec-1). NIDCM (T2DM+) demonstrated decreased GCPS and GLPS in the no/mild subgroup, reduced LV GCPS, GLPS, and longitudinal PDSR in the moderate subgroup, and reduced GRPS, GCPS, GLPS, and longitudinal PDSR in the severe subgroup compared with NIDCM (T2DM-) patients. Multivariable regression analysis identified that mitral regurgitation severity (ß = -0.13, 0.15, and 0.25 for GRPS, GCPS, and GLPS) and the presence of T2DM (ß = 0.14 and 0.13 for GCPS and GLPS) were independent determinants of LV strains in NIDCM patients. DATA CONCLUSION: Increased mitral regurgitation severity is associated with reduced LV strains in NIDCM patients with T2DM. The presence of T2DM exacerbated the decline of LV function across various mitral regurgitation levels in NIDCM patients, resulting in reduced LV strains. TECHNICAL EFFICACY: Stage 3.

Left Atrial Phasic Function Impairment in Subacute and Chronic Pulmonary Embolism Patients With Different Degrees of Obstruction: An MRI Feature Tracking Study.

BACKGROUND: The alteration of left atrial (LA) phasic function in subacute and chronic pulmonary embolism (PE) patients is unclear. PURPOSE: To investigate LA phasic strain and LA-right ventricular (RV) interaction in subacute and chronic PE patients with different degrees of obstruction by MRI-feature tracking (MRI-FT). STUDY TYPE: Retrospective. POPULATION: One hundred three PE patients (54 subacute [2 weeks to 3 months after initial symptoms], 49 chronic [>3 months after initial symptoms]) and 80 controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady state free precession sequence. ASSESSMENT: Patients were divided into mild (pulmonary artery obstruction index [PAOI] < 30%, N = 57), moderate (30% ≤ PAOI < 50%, N = 27), and severe (50% ≥ PAOI, N = 19) PE subgroups. LA reservoir, conduit, and active pump longitudinal strains (εs, εe, and εa) and strain rates (SRs, SRe, and SRa) and biventricular global strains were measured. Determinants of LA strains were investigated. STATISTICAL TESTS: ANOVA, t-tests, Mann-Whitney U tests, linear regression. P < 0.05 was considered statistically significant. RESULTS: For both subacute and chronic PE patients, LA reservoir, conduit, and active pump strains and strain rates were significantly lower than in controls. However, there were no significant differences in LA strains between patients with subacute and chronic PE (P = 0.933, 0.625, and 0.630 for εs, εe, and εa). The severe PE subgroup had significantly higher εa and SRa than the mild and moderate PE subgroups. LA strains were significantly correlated with RV diameter and biventricular strains, and RV diameter (ß = -6.836, -4.084, and -1.899 for εs, εe, and εa) was independently associated with LA strains after adjustment for other factors (R2 = 0.627, 0.536, and 0.437 for εs, εe, and εa). DATA CONCLUSION: LA phasic function evaluated by MRI-FT was significantly impaired in subacute and chronic PE patients, and LA active pump function in the severe PE subgroup was higher than that in the mild and moderate PE subgroups. The independent association between RV diameter and LA strains demonstrates that RV diameter may be an important indicator for monitoring LA dysfunction in PE patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Artificial intelligence iterative reconstruction in abdominal CT of patients with irregular arm positioning: a case-by-case evaluation.

BACKGROUND: Streak artifacts induced by irregular arm positioning have been an issue in diagnosing the abdomen. PURPOSE: To illustrate the risk of misdiagnosis in abdominal computed tomography (CT) of patients with irregular arm positioning through a case-by-case evaluation and to test if it can be solved by the artificial intelligence iterative reconstruction (AIIR) algorithm. MATERIAL AND METHODS: By reviewing 5220 cases of chest and thoracoabdominal CT, 64 patients with irregular arm positioning were enrolled, whose image data were reconstructed using AIIR in addition to routine hybrid iterative reconstruction (HIR). Lesion detection for livers, spleens, kidneys, gallbladders, and pancreas on AIIR images, performed by two radiologists, was compared with those on HIR images. Discrepancies arising from AIIR images included both cases with additional abnormalities and those with corrections made on previous detections. For cases with discrepancies, artifact scores for organs where discrepancies were found, and contrast-to-noise ratios (CNRs) of cysts with discrepancies were compared between two image sets. RESULTS: Additional abnormalities were detected for 15 cases: additional liver cirrhosis (n=2); additional gallbladder stone (n=1); additional cholecystitis (n=1), additional spleen nodule (n=1); additional kidney cysts (n=8); additional liver cysts (3); and additional spleen cyst (n=1). A spleen contusion was corrected for one case. All involved artifact scores were improved on AIIR images. CNRs of involved liver, kidney, and spleen cysts were improved by up to 539.7%, 538.5%, and 245.5%, respectively. CONCLUSION: Irregular arm positioning may induce a variety of misdiagnoses in abdominal CT, which is almost totally avoidable by the AIIR algorithm.

Unveiling long COVID symptomatology, co-occurrence trends, and symptom distress post SARS-CoV-2 infection.

BACKGROUND: Long COVID, an emerging public health issue, is characterized by persistent symptoms following SARS-CoV-2 infection. This study aims to explore the relationship between post-COVID-19 symptomatology and patient distress employing Latent Class Analysis to uncover symptom co-occurrence patterns and their association with distress. METHODS: A cross-sectional study was conducted using an online survey among 240 participants from a university and affiliated hospital of southern Taiwan. The survey quantified distress due to persistent symptoms and assessed the prevalence of Long COVID, symptom co-occurrence, and latent symptom classes. Latent Class Analysis (LCA) identified distinct symptom patterns, and multiple regression models evaluated associations between symptom patterns, distress, and demographic factors. RESULTS: The study found that 80 % of participants experienced Long COVID, with symptoms persisting for over three months. Individuals with multiple COVID-19 infections showed a significant increase in general (ß = 1.79), cardiovascular (ß = 0.61), and neuropsychological symptoms (ß = 2.18), and higher total distress scores (ß = 6.35). Three distinct symptomatology classes were identified: "Diverse", "Mild", and "Severe" symptomatology. The "Mild Symptomatology" class was associated with lower distress (-10.61), while the "Severe Symptomatology" class showed a significantly higher distress due to symptoms (13.32). CONCLUSION: The study highlights the significant impact of Long COVID on individuals, with distinct patterns of symptomatology and associated distress. It emphasizes the cumulative effect of multiple COVID-19 infections on symptom severity and the importance of tailored care strategies.

Barley Protein LFBEP-C1 from Lactiplantibacillus plantarum dy-1 Fermented Barley Extracts by Inhibiting Lipid Accumulation in a Caenorhabditis elegans Model.

Objective: This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans (C. elegans). Methods: In this study, the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C. elegans. The worms were fed Escherichia coli OP50 ( E. coli OP50), glucose, and different concentrations of LFBEP-C1. Body size, lifespan, movement, triglyceride content, and gene expression were analyzed. The results were analyzed using ANOVA and Tukey's multiple comparison test. Results: Compared with the model group, the head-swing frequency of C. elegans in the group of LFBEP-C1 at 20 µg/mL increased by 33.88%, and the body-bending frequency increased by 27.09%. This indicated that LFBEP-C1 improved the locomotive ability of C. elegans. The average lifespan of C. elegans reached 13.55 days, and the body length and width of the C. elegans decreased after LFBEP-C1 intake. Additionally, LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels. The expression levels of sbp-1, daf-2, and mdt-15 significantly decreased, while those of daf-16, tph-1, mod-1, and ser-4 significantly increased after LFBEP-C1 intake. Changes in these genes explain the signaling pathways that regulate lipid metabolism. Conclusion: LFBEP-C1 significantly reduced lipid deposition in C. elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development, lifespan, and exercise behavior of C. elegans. In addition, LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein, insulin, and 5-hydroxytryptamine signaling pathways.

Effect of cytochrome P450 3A4 on tissue distribution of humantenmine, koumine, and gelsemine, three alkaloids from the toxic plant Gelsemium.

Humantenmine, koumine, and gelsemine are three indole alkaloids found in the highly toxic plant Gelsemium. Humantenmine was the most toxic, followed by gelsemine and koumine. The aim of this study was to investigate and analyze the effects of these three substances on tissue distribution and toxicity in mice pretreated with the Cytochrome P450 3A4 (CYP3A4) inducer ketoconazole and the inhibitor rifampicin. The in vivo test results showed that the three alkaloids were absorbed rapidly and had the ability to penetrate the blood-brain barrier. At 5 min after intraperitoneal injection, the three alkaloids were widely distributed in various tissues and organs, the spleen and pancreas were the most distributed, and the content of all tissues decreased significantly at 20 min. Induction or inhibition of CYP3A4 in vivo can regulate the distribution and elimination effects of the three alkaloids in various tissues and organs. Additionally, induction of CYP3A4 can reduce the toxicity of humantenmine, and vice versa. Changes in CYP3A4 levels may account for the difference in toxicity of humantenmine. These findings provide a reliable and detailed dataset for drug interactions, tissue distribution, and toxicity studies of Gelsemium alkaloids.

Counteracting TGM2 by a Fibroin peptide ameliorated Adriamycin-induced nephropathy via regulation of lipid metabolism through PANX1-PPAR α/PANK1 pathway.

Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence 'YEVEDYR') from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to ß-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown in vivo increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. In vitro, overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.

Study on 2D Molecular Networks of Flexible Pentacarboxylic Acid Ligands Induced by Ether Bonds in Response to Selective Guest Inclusion.

The flexibility of ligands allows for their bending, twisting, or rotation to adopt various conformations, leading to distinct symmetries during the self-assembled process. Flexible aromatic acid ligands modified by ether bonds are a promising type of self-assembled module when it comes to surfaces. Here, two pentacarboxylic acid ligands (H5L1 and H5L2) with minor skeleton differences have successfully self-assembled into disparate porous networks on the graphite surface and demonstrated excellent potential for the inclusion of guest molecules. The H5L1 molecule's network structure only accommodates coronene (COR) molecules. With fewer COR molecules, H5L1 molecules act as a host template to accommodate the COR molecules. When there are too many COR molecules, COR molecules will induce H5L1 molecules to transform into a new host-guest nanostructure. Additionally, H5L2 molecules showed the ability to capture C70 molecules and exhibited cavity selectivity. However, the assembled network of H5L2 was slightly deformed in attempts to trap the COR molecules. To understand these phenomena more deeply, various assembled mechanisms were analyzed in combination with building theoretical models and energy analysis. These results reveal the great potential of flexible aromatic acid ligands in two-dimensional self-assembly and host-guest systems for their application in related fields.

Mitochondria-localizing triphenylphosphine-8-hydroxyquinoline Ru complexes induce ferroptosis and their antitumor evaluation.

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 âˆ¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 âˆ¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.

Accumulation of ß-aminoisobutyric acid mediates hyperalgesia in ovariectomized mice through Mas-related G protein-coupled receptor D signaling.

Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. ß-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women.

Impact of Type 2 Diabetes Mellitus on Left Atrioventricular Coupling and Left Atrial Deformation in Patients with Essential Hypertension: An MRI Feature Tracking Study.

BACKGROUND: Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are both associated with left ventricular (LV) and left atrial (LA) structural and functional abnormalities; however, the relationship between the left atrium and ventricle in this population is unclear. PURPOSE: To identify differences between hypertensive patients with and without T2DM as the basis for further investigation the atrioventricular coupling relationship. STUDY TYPE: Cross-sectional, retrospective study. POPULATION: 89 hypertensive patients without T2DM [HTN (T2DM-)] (age: 58.4 +/- 11.9 years, 48 male), 62 hypertensive patients with T2DM [HTN (T2DM+)] (age: 58.5 +/- 9.1 years, 32 male) and 70 matched controls (age: 55.0 +/- 9.6 years, 37 male). FIELD STRENGTH/SEQUENCE: 2D balanced steady-state free precession cine sequence at 3.0 T. ASSESSMENT: LA reservoir, conduit, and booster strain (εs, εe, and εa) and strain rate (SRs, SRe, and SRa), LV radial, circumferential and longitudinal peak strain (PS) and peak systolic strain rate and peak diastolic strain rate (PSSR and PDSR) were derived from LA and LV cine images and compared between groups. STATISTICAL TESTS: Chi-square or Fisher's exact test, one-way analysis of variance, analysis of covariance, Pearson's correlation, multivariable linear regression analysis, and intraclass correlation coefficient. A P value <0.05 was considered significant. RESULTS: Compared with controls, εs, εe, SRe and PS-longitudinal, PDSR-radial, and PDSR-longitudinal were significantly lower in HTN (T2DM-) group, and they were even lower in HTN (T2DM+) group than in both controls and HTN (T2DM-) group. SRs, εa, SRa, as well as PS-radial, PS-circumferential, PSSR-radial, and PSSR-circumferential were significantly lower in HTN (T2DM+) compared with controls. Multivariable regression analyses demonstrated that: T2DM and PS-circumferential and PS-longitudinal (ß = -4.026, -0.486, and -0.670, respectively) were significantly associated with εs; T2DM and PDSR-radial and PDSR-circumferential were significantly associated with εe (ß = -3.406, -3.352, and -6.290, respectively); T2DM and PDSR-radial were significantly associated with SRe (ß = 0.371 and 0.270, respectively); T2DM and PDSR-longitudinal were significantly associated with εa (ß = -1.831 and 5.215, respectively); and PDSR-longitudinal was significantly associated with SRa (ß = 1.07). DATA CONCLUSION: In hypertensive patients, there was severer LA dysfunction in those with coexisting T2DM, which may be associated with more severe LV dysfunction and suggests adverse atrioventricular coupling. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of pathophysiological bases of airway inflammation and its anti-inflammatory response. Aberrant mitochondrial signaling and mitochondrial dysfunction underlie the pathomechanisms leading to COPD. This study aims to investigate the effects of the Yiqigubiao (YQGB) pill, a traditional Chinese medicine (TCM), on Sirtuin 5 (SIRT5) and mitochondrial function in patients with COPD. Methods: Thirty-four patients with COPD were randomized into oral YQGB or placebo groups concurrent with a 24-week routine treatment. The pulmonary function was assessed by examining the levels of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), FEV1, and FVC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect SIRT5 expression in mitochondria isolated from peripheral blood. Flow cytometry was used to detect changes in mitochondrial membrane potential and reactive oxygen species (ROS) in peripheral blood lymphocytes. Human bronchial epithelial (HBE) cells stimulated by cigarette smoke extract (CSE) were treated with YQGB. After SIRT5 was knocked down in cells, the changes in mitochondrial membrane potential, levels of adenosine triphosphate (ATP), and ROS were detected. Results: YQGB treatment significantly improved lung function in patients with COPD. The expression of SIRT5 and the mitochondrial membrane potential significantly increased and ROS decreased in patients with COPD after YQGB treatment. The CSE decreased cell proliferation and SIRT5 expression, which was alleviated after YQGB treatment. Furthermore, SIRT5 was knocked down in CSE-stimulated HBE cells, and its expression was elevated upon YQGB treatment. The knockdown of SIRT5 significantly altered the CSE-stimulation-induced dysregulation of mitochondrial membrane potential, ATP levels, and ROS. This was also restored after YQGB treatment. Conclusions: YQGB treatment can elevate SIRT5 expression, restore mitochondrial function in COPD, and exert protective effects.

Nomogram prediction of vessels encapsulating tumor clusters in small hepatocellular carcinoma ≤ 3 cm based on enhanced magnetic resonance imaging.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma (HCC). However, it seems that no one have focused on predicting VETC status in small HCC (sHCC). This study aimed to develop a new nomogram for predicting VETC positivity using preoperative clinical data and image features in sHCC (≤ 3 cm) patients. AIM: To construct a nomogram that combines preoperative clinical parameters and image features to predict patterns of VETC and evaluate the prognosis of sHCC patients. METHODS: A total of 309 patients with sHCC, who underwent segmental resection and had their VETC status confirmed, were included in the study. These patients were recruited from three different hospitals: Hospital 1 contributed 177 patients for the training set, Hospital 2 provided 78 patients for the test set, and Hospital 3 provided 54 patients for the validation set. Independent predictors of VETC were identified through univariate and multivariate logistic analyses. These independent predictors were then used to construct a VETC prediction model for sHCC. The model's performance was evaluated using the area under the curve (AUC), calibration curve, and clinical decision curve. Additionally, Kaplan-Meier survival analysis was performed to confirm whether the predicted VETC status by the model is associated with early recurrence, just as it is with the actual VETC status and early recurrence. RESULTS: Alpha-fetoprotein_lg10, carbohydrate antigen 199, irregular shape, non-smooth margin, and arterial peritumoral enhancement were identified as independent predictors of VETC. The model incorporating these predictors demonstrated strong predictive performance. The AUC was 0.811 for the training set, 0.800 for the test set, and 0.791 for the validation set. The calibration curve indicated that the predicted probability was consistent with the actual VETC status in all three sets. Furthermore, the decision curve analysis demonstrated the clinical benefits of our model for patients with sHCC. Finally, early recurrence was more likely to occur in the VETC-positive group compared to the VETC-negative group, regardless of whether considering the actual or predicted VETC status. CONCLUSION: Our novel prediction model demonstrates strong performance in predicting VETC positivity in sHCC (≤ 3 cm) patients, and it holds potential for predicting early recurrence. This model equips clinicians with valuable information to make informed clinical treatment decisions.