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1.
Heliyon ; 10(8): e28814, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-39360019

ABSTRACT

[This corrects the article DOI: 10.1016/j.heliyon.2024.e24428.].

2.
Rhinology ; 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39365558

ABSTRACT

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic sinonasal disease characterized by heterogeneous inflammation. However, the presence of systemic inflammation heterogeneity in CRSwNP patients remains unknown. This study aims to profile transcriptomic alterations in the blood of CRSwNP patients and characterize the CRSwNP heterogeneity based on blood transcriptomic biomarkers. METHODOLOGY: Patients with CRSwNP were prospectively recruited from three hospitals and chronologically divided into exploratory (n=123) and independent validation (n=46) cohorts. Transcriptomic profiles were generated by whole blood mRNA sequencing and subjected to patient clustering, differential expression, and pathway analysis. Differences in immune pattern and clinicopathologic features between clusters were assessed. A transcriptomic signature was defined and applied to an independent cohort to validate the findings. RESULTS: CRSwNP patients showed diverse blood transcriptomic profiles versus healthy controls, or when stratified by tissue and blood eosinophils and asthma comorbidity. Transcriptome-wide correlation analysis revealed a transcriptional signature associated with blood eosinophil levels, consisting of nine T2-related genes (CLC, SIGLEC8, ALOX15, IL5RA, PTGDR2, CCL23, CCR3, EPX and IL1RL1). Three distinct clusters with differing systemic eosinophilic and neutrophilic inflammation patterns and asthma comorbidity were identified based on transcriptomic profiling of T2 and T1/3-related blood biomarkers. A 36-gene signature was developed by machine learning and accurately predicted the three CRSwNP subtypes. Validation on an independent cohort confirmed the prediction robustness. CONCLUSIONS: There is heterogeneous systemic inflammation associated with eosinophilic and neutrophilic patterns in patients with CRSwNP. Endotyping based on blood transcriptomic biomarkers might lead to more personalized treatment strategies for CRSwNP in the future.

3.
Article in English | MEDLINE | ID: mdl-39344277

ABSTRACT

OBJECTIVE: To compare the diagnostic performance of different manufacturers' immunoassays for the soluble fms-like tyrosine kinase-1 (sFlt-1)-to-placental growth factor (PlGF) ratio with that of a point-of-care test for glycosylated fibronectin (GlyFn) in women with suspected pre-eclampsia (PE). METHODS: This was a prospective, single-center, double-blinded, non-interventional study of East Asian women with a singleton pregnancy who presented with hypertension with or without clinical features of PE after 20 weeks' gestation between January 2020 and March 2022. Maternal serum samples were collected at the time of presentation, and subsequent management followed the departmental protocol, based on gestational age, severity of hypertension, fetal condition and presence of severe PE features. Women diagnosed with PE at presentation were excluded. PE was diagnosed according to the 2018 International Society for the Study of Hypertension in Pregnancy classification. Levels of sFlt-1 and PlGF were measured using the Cobas e411 (Roche Diagnostics), BRAHMS KRYPTOR (ThermoFisher Scientific) and iMAGIN 1800 (Ningbo-Aucheer) platforms. GlyFn levels were measured using the Lumella™ GlyFn PoC test (Diabetomics). The predictive performance of each test to rule out PE within 7 days and rule in PE within 28 days from the date of presentation was assessed. Based on the PROGNOSIS study, a sFlt-1/PlGF ratio of ≤ 38 on the Roche platform was used to predict the absence of PE within 7 days. The sFlt-1/PlGF ratio was classified as high or low using platform-specific thresholds equivalent to a Roche sFlt-1/PlGF ratio of 38, which were derived using Passing-Bablok regression. GlyFn was categorized as high or low using two reported clinical management thresholds (263 µg/mL and 510 µg/mL). RESULTS: Overall, 236 women with suspected PE were included, of whom 70 (29.7%) were diagnosed with PE; 36 (51.4%) and 70 (100%) developed PE within 7 days and 28 days, respectively. Eighty-eight (37.3%) women had a sFlt-1/PlGF ratio of > 38 on the Roche platform, 79 (33.5%) women had a sFlt-1/PlGF ratio of > 55 on the KRYPTOR platform and 96 (40.7%) women had a sFlt-1/PlGF ratio of > 40 on the iMAGIN 1800 platform. Furthermore, 62 (26.3%) and four (1.7%) women had a GlyFn level of > 263 µg/mL and > 510 µg/mL, respectively. The negative predictive value (NPV) of the sFlt-1/PlGF ratio measured on the Roche, KRYPTOR and iMAGIN 1800 platforms to rule out PE within 7 days after presentation was 83.3%, 82.0% and 82.9%, respectively, while that for GlyFn > 263 µg/mL and > 510 µg/mL was 82.6% and 70.4%, respectively. The corresponding positive predictive values (PPV) to rule in PE within 28 days after presentation were 50.5%, 52.3% and 46.7%, respectively, for the sFlt-1/PlGF ratio, and 35.4% and 50.0%, respectively, for GlyFn > 263 µg/mL and > 510 µg/mL. CONCLUSIONS: The predictive performance of different manufacturers' assays for the sFlt-1/PlGF ratio to rule in and rule out PE were similar once standardized to a common threshold. Our findings suggest that the sFlt-1/PlGF ratio and GlyFn using a cut-off of 263 µg/mL can both be utilized to rule out PE within 7 days after assessment, with a moderate NPV. The PPV for ruling in PE within 28 days remains poor. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

4.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 59(10): 977-987, 2024 Sep 27.
Article in Chinese | MEDLINE | ID: mdl-39344448

ABSTRACT

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients'suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aimsto establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. Temporomandibular joint disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

6.
medRxiv ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39314938

ABSTRACT

Motivation: The clinical success of brain-machine interfaces depends on overcoming both biological and material challenges to ensure a long-term stable connection for neural recording and stimulation. Therefore, there is a need to quantify any damage that microelectrodes sustain when they are chronically implanted in the human cortex. Methods: Using scanning electron microscopy (SEM), we imaged 980 microelectrodes from Neuroport arrays chronically implanted in the cortex of three people with tetraplegia for 956-2246 days. We analyzed eleven multi-electrode arrays in total: eight arrays with platinum (Pt) electrode tips and three with sputtered iridium oxide tips (SIROF); one Pt array was left in sterile packaging, serving as a control. The arrays were implanted/explanted across three different clinical sites surgeries (Caltech/UCLA, Caltech/USC and APL/Johns Hopkins) in the anterior intraparietal area, Brodmann's area 5, motor cortex, and somatosensory cortex.Human experts rated the electron micrographs of electrodes with respect to five damage metrics: the loss of metal at the electrode tip, the amount of separation between the silicon shank and tip metal, tissue adherence or bio-material to the electrode, damage to the shank insulation and silicone shaft. These metrics were compared to functional outcomes (recording quality, noise, impedance and stimulation ability). Results: Despite higher levels of physical degradation, SIROF electrodes were twice as likely to record neural activity than Pt electrodes (measured by SNR), at the time of explant. Additionally, 1 kHz impedance (measured in vivo prior to explant) significantly correlated with all physical damage metrics, recording, and stimulation performance for SIROF electrodes (but not Pt), suggesting a reliable measurement of in vivo degradation.We observed a new degradation type, primarily occurring on stimulated electrodes ("pockmarked" vs "cracked") electrodes; however, tip metalization damage was not significantly higher due to stimulation or amount of charge. Physical damage was centralized to specific regions of an array often with differences between outer and inner electrodes. This is consistent with degradation due to contact with the biologic milieu, influenced by variations in initial manufactured state. From our data, we hypothesize that erosion of the silicon shank often precedes damage to the tip metal, accelerating damage to the electrode / tissue interface. Conclusions: These findings link quantitative measurements, such as impedance, to the physical condition of the microelectrodes and their capacity to record and stimulate. These data could lead to improved manufacturing or novel electrode designs to improve long-term performance of BMIs making them are vitally important as multi-year clinical trials of BMIs are becoming more common.

7.
Public Health ; 236: 396-403, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39303628

ABSTRACT

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Suboptimal health status (SHS) is a third state between health and disease. Long-term being SHS will be detrimental to one's ability development. Previous studies have demonstrated the associations of lifestyle behaviors or work stress with SHS, but few studies have comprehensively analyzed the underlying factors and mechanisms between the three. This study aimed to investigate whether lifestyle behaviors mediated the relationship between self-perceived work stress and SHS. METHODS: A total of 4238 urban workers, who participated in a cross-sectional survey conducted from December 2018 to October 2019, were included. A general linear model was used to explore the associations between lifestyle behaviors and self-perceived work stress with SHS after adjusting for demographic variables. Structural equation modeling was performed to examine the mediation by lifestyle behaviors. RESULTS: The mean transformed scores of physical, mental, and social SHS were 70.98, 67.17, and 61.72, respectively. Unhealthy lifestyle behaviors and high self-perceived work stress positively affected SHS (P < 0.001). Self-perceived work stress imposed negative effects on physical SHS (ß = -0.228, P < 0.001), mental SHS (ß = -0.237, P < 0.001), and social SHS (ß = -0.092, P < 0.001). The indirect effects of self-perceived work stress on physical SHS (ß = -0.139, 95% CI: -0.178 to -0.106), mental SHS (ß = -0.106, 95% CI: -0.134 to -0.082), and social SHS (ß = -0.121, 95% CI: -0.154 to -0.092) were statistically significant. CONCLUSIONS: Lifestyle behaviors and self-perceived work stress were significantly associated with SHS among Chinese urban workers. The mediating effects of unhealthy lifestyle behaviors were found in the relationship between high self-perceived work stress and SHS. Future longitudinal research may verify these associations and elucidate the underlying mechanisms.

8.
Ann Oncol ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39293515

ABSTRACT

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) that progresses on androgen receptor pathway inhibitors (ARPIs) may continue to be driven by AR signaling. BMS-986365 is an orally administered ligand-directed degrader targeting the AR via a first-in-class dual mechanism of AR degradation and antagonism. CC-94676-PCA-001 (NCT04428788) is a phase 1 multicenter study of BMS-986365 in patients with progressive mCRPC. PATIENTS AND METHODS: Patients who progressed on androgen deprivation therapy, ≥ 1 ARPI, and taxane chemotherapy (unless declined/ineligible) were enrolled. The study included dose escalation (Part A) and expansion (Part B) of BMS-986365 up to 900 mg twice daily (BID). Primary objectives were safety, tolerability, and to define maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Key secondary endpoints included decline in prostate-specific antigen ≥50% (PSA50) and radiographic progression-free survival (rPFS). RESULTS: Parts A and B enrolled 27 and 68 patients, respectively. In Part B, the median number of prior therapies was 4 (range 2-11). The most common treatment-related adverse events (TRAEs) were asymptomatic prolonged corrected QT interval (47%) and bradycardia (34%). Part A MTD was not reached and RP2D selection is ongoing. Across Part B three highest doses (400-900 mg BID, n = 60), PSA50 was 32% (n = 19), including 50% (n = 10/20) at 900 mg; median rPFS (95% CI) was 6.3 months (5.3-12.6), including 8.3 months (3.8-16.6) at 900 mg; and rPFS was longer in patients without versus with prior chemotherapy: 16.5 months (5.5-not evaluable) versus 5.5 months (2.7-8.3), respectively. Efficacy was observed in patients with AR ligand binding domain (LBD) WT or with AR LBD mutations. CONCLUSIONS: BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with potentially higher benefit in chemotherapy-naïve patients. These data show BMS-986365's potential to overcome resistance to current ARPIs, regardless of AR LBD mutation status.

9.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(8): 1431-1440, 2024 Aug 20.
Article in Chinese | MEDLINE | ID: mdl-39276038

ABSTRACT

OBJECTIVE: To explore the effects of Qingshen Granules (QSG) on adenine-induced renal fibrosis in mice and in uric acid (UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes, miR-330-3p and CREBBP. METHODS: A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks. An adenoassociated virus vector was injected into the tail vein, and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9, Hsp70, and TSG101 and expressions of Col-III, α-SMA, FN, and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining. In the cell experiment, NRK-49F cells were stimulated with uric acid (400 µmol/L) followed by treatment with QSG-medicated serum from SD rats, and the changes in expressions of the exosomal markers and Col-III, α-SMA, FN, and E-cad were analyzed. Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP, whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells. RESULTS: The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9, Hsp70, and TSG101, which were decreased by treatment with QSG. The expressions of Col-III, α-SMA, and FN increased and Ecad decreased in the mouse models but these changes were reversed by QSG treatment. QSG treatment obviously alleviated renal fibrosis in the mouse models. Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p, increased CREBBP levels, and reduced fibrosis in the mouse models. Dual luciferase assay confirmed CREBBP as a target of miR-330-3p, which was consistent with the results of the cell experiments. CONCLUSION: QSG inhibits renal fibrosis in mice by regulating the exosomes, reducing miR-330-3p levels, and increasing CREBBP expression.


Subject(s)
Exosomes , Fibrosis , Kidney , MicroRNAs , Animals , Exosomes/metabolism , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Kidney/pathology , Kidney/metabolism , CREB-Binding Protein/metabolism , CREB-Binding Protein/genetics , Kidney Diseases/metabolism , Kidney Diseases/chemically induced , Drugs, Chinese Herbal/pharmacology , Adenine , Rats , Male , Uric Acid , Cell Line
10.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(9): 807-814, 2024 Sep 12.
Article in Chinese | MEDLINE | ID: mdl-39266478

ABSTRACT

Objective: To analyze the clinical characteristics of asthmatic children with persistent airflow limitation (PAL) in order to improve understanding of PAL and improve asthma management. Methods: The clinic data of asthmatic children aged 6 to 18 years with and without PAL, who visited the Department of Allergy at Children's Hospital of the Capital Institute of Pediatrics between January 2021 and June 2023, were analyzed retrospectively. The study included a total of 197 patients (153 males and 44 females), with a median age of 9.0 (7.0, 12.0) years. The analysis encompassed demographic features, disease-related factors, laboratory tests, and spirometry parameters. Quantitative data differences between the two groups were assessed using the Student's t-test or the Mann-Whitney U test. Qualitative data comparisons were made using the Chi-square test or Fisher's exact test. Results: This study included 100 non-PAL and 97 PAL patients. The female-to-male ratio in the two groups was 27/73 and 17/80, respectively. Age and BMI were 11.0 (10.0, 13.0) years and 20.3 (17.7, 24.1) kg/m2 in the PAL group, which was significantly higher than in the non-PAL group (P<0.001). Among the PAL group, 49.5% fell within the 9-12 age group. The PAL group had a higher percentage of patients with an asthma duration of more than 3 years (89.7% vs. 62.0%, P<0.001) and a history of pneumonia (13.4% vs. 4.0%, P=0.036) compared to the non-PAL group. Regarding laboratory tests, a higher percentage of patients in the PAL group had an elevated FeNO level (60.9% vs. 37.6%, P=0.002) and animal sensitization (50.7% vs. 30.7%, P=0.022) compared to the non-PAL group. Of the 69 patients who underwent spirometry before and after PAL development, FEV1%pred, FEV1/FVC, and MMEF%pred values gradually decreased, with a significant decline in the year preceding PAL development. Conclusions: Asthmatic children with PAL had characteristics such as relatively older age, higher BMI, longer duration of asthma, eosinophilic inflammation, and atopy. Lung function decline occurred several years before PAL development. Long-term follow-up should focus on the evolving trend of spirometry parameters.


Subject(s)
Asthma , Spirometry , Humans , Child , Asthma/physiopathology , Asthma/diagnosis , Male , Female , Retrospective Studies , Adolescent , Forced Expiratory Volume , Respiratory Function Tests
11.
Benef Microbes ; : 1-20, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39242081

ABSTRACT

The neuropsychiatric effects of probiotics, prebiotics, and synbiotics have been gaining attention since the rise of microbial-gut-brain axis research. Nevertheless, some of the findings are inconsistent, and few studies have analysed the similarities and differences in the neuropsychiatric effects of the three comprehensively. To reveal the respective neuropsychiatric effects of probiotics, prebiotics, and synbiotics and synthesise the similarities and differences among the three effects, 47 meta-analyses with 12 types of neuropsychiatric results were integrated under an umbrella review. Probiotics, prebiotics, and synbiotics intake might all be associated with improvements in some neuropsychiatric outcomes, including neuropsychological test outcomes (probiotic and prebiotic), hepatic encephalopathy outcomes (probiotic, prebiotic, and synbiotic), instant memory in patients with Alzheimer's disease (probiotic), depressive symptoms (probiotic, prebiotic and synbiotic), mood states and psychiatric distress (probiotic), overall mental health (probiotic), neurological function (probiotic), brain-derived neurotrophic factor (BDNF) concentration (probiotic and synbiotic), and Pittsburgh Sleep Quality Index (PSQI) score (probiotic). All three are similar in that the intake of probiotics, prebiotics, and synbiotics might be associated with improvements in hepatic encephalopathy outcomes and depressive symptoms, both probiotic and synbiotic intake might be associated with elevated BDNF concentrations, and both probiotic and prebiotic intake might be associated with improved neuropsychological test results. The difference between the three is that the neuropsychiatric effects of probiotics might be more widespread and be reflected in the fact that probiotic intake might also be associated with improvements in mood states and psychiatric distress, overall mental health, neurological function, Alzheimer's disease patients' instant memory, and PSQI score. Probiotics might be the best and most promising option for improving neuropsychiatric outcomes. In the future, in addition to requiring more high-quality meta-analyses, further preclinical studies are needed to explore specific relevant mechanisms and determine true causal relationships.

12.
Ann Oncol ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39293516

ABSTRACT

BACKGROUND: Homozygous deletion of methylthioadenosine phosphorylase (MTAP) occurs in ∼10%-15% of solid tumors. AMG 193, a CNS-penetrant methylthioadenosine-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, selectively induces synthetic lethality in MTAP-deleted tumor cells. Here, we report results of the completed monotherapy dose exploration evaluating AMG 193 in patients with MTAP-deleted solid tumors. PATIENTS AND METHODS: In this first-in-human, multicenter, open-label, phase I study, patients with advanced CDKN2A-deleted and/or MTAP-deleted solid tumors received AMG 193 orally [once (o.d.) or twice (b.i.d.) daily] continuously in 28-day cycles. Primary objectives were safety and tolerability assessed by dose-limiting toxicities and determination of the maximum tolerated dose; secondary objectives included pharmacokinetics and preliminary antitumor activity measured by RECIST v1.1. RESULTS: As of 23 May 2024, 80 patients in dose exploration received AMG 193 at doses 40-1600 mg o.d. or 600 mg b.i.d. The most common treatment-related adverse events were nausea (48.8%), fatigue (31.3%), and vomiting (30.0%). Dose-limiting toxicities were reported in eight patients at doses ≥240 mg, including nausea, vomiting, fatigue, hypersensitivity reaction, and hypokalemia. The maximum tolerated dose was determined to be 1200 mg o.d. Mean exposure of AMG 193 increased in a dose-proportional manner from 40 mg to 1200 mg. Among the efficacy-assessable patients treated at the active and tolerable doses of 800 mg o.d., 1200 mg o.d., or 600 mg b.i.d. (n = 42), objective response rate was 21.4% (95% confidence interval 10.3% to 36.8%). Responses were observed across eight different tumor types, including squamous/non-squamous non-small-cell lung cancer, pancreatic adenocarcinoma, and biliary tract cancer. At doses ≥480 mg, complete intratumoral PRMT5 inhibition was confirmed in paired MTAP-deleted tumor biopsies, and molecular responses (circulating tumor DNA clearance) were observed. CONCLUSIONS: AMG 193 demonstrated a favorable safety profile without clinically significant myelosuppression. Encouraging antitumor activity across a variety of MTAP-deleted solid tumors was observed based on objective response rate and circulating tumor DNA clearance.

13.
Br Dent J ; 237(6): 433, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39333795
14.
Chem Sci ; 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39246344

ABSTRACT

The assembly of discrete superatomic nanoclusters into larger constructs is a significant stride towards developing a new set of artificial/pseudo-elements. Herein, we describe a novel series of 16-electron supermolecules derived from the combination of discrete 8-electron superatomic synthons containing interstitial hydrides as vertex-sharing building blocks. The symmetric (RhH)2Ag33[S2P(OPr)2]17 (1) and asymmetric PtHPtAg32[S2P(OPr)2]17 (2) are characterized by ESI-MS, SCXRD, NMR, UV-vis absorption spectra, electrochemical and computational methods. Cluster 1 represents the first group 9-doped 16-electron supermolecule, composed of two icosahedral (RhH)@Ag12 8-electron superatoms sharing a silver vertex. Cluster 2 results from the assembly of two distinct icosahedral units, Pt@Ag12, and (PtH)@Ag12. In both cases, the presence of the interstitial hydrides is unprecedented. The stability of the supermolecules is investigated, and 2 spontaneously transforms into Pt2Ag33[S2P(OPr)2]17 (3) with thermal treatment. The lability of the hydride within the icosahedral framework in solution at low-temperature was confirmed by the VT-NMR.

15.
Molecules ; 29(18)2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39339425

ABSTRACT

The ability to fabricate bimetallic clusters with atomic precision offers promising prospects for elucidating the correlations between their structures and properties. Nevertheless, achieving precise control at the atomic level in the production of clusters, including the quantity of dopant, characteristic of ligands, charge state of precursors, and structural transformation, have remained a challenge. Herein, we report the synthesis, purification, and characterization of a new bimetallic hydride cluster, [AuCu11(H){S2P(OiPr)2}6(C≡CPh)3] (AuCu11H). The hydride position in AuCu11H was determined using DFT calculations. AuCu11H comprises a ligand-stabilized defective fcc Au@Cu11 cuboctahedron. AuCu11H is metastable and undergoes a spontaneous transformation through ligand exchange into the isostructural [AuCu11(Cl){S2P(OiPr)2}6(C≡CPh)3] (AuCu11Cl) and into the complete cuboctahedral [AuCu12{S2P(OiPr)2}6(C≡CPh)4]+ (AuCu12) through an increase in nuclearity. These structural transformations were tracked by NMR and mass spectrometry.

16.
Eur Rev Med Pharmacol Sci ; 28(15): 4046-4059, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39194200

ABSTRACT

OBJECTIVE: A metabolism score for visceral fat (METS-VF) is an innovative method to access abdominal fat and visceral fat. So far, the relationship between the METS-VF index and chronic obstructive pulmonary disease (COPD) has remained unclear. We investigated the relationship between the METS-VF index and COPD prevalence utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. PATIENTS AND METHODS: A binary logistic regression analysis was performed using NHANES 2007-2018 data to assess the relationship between the METS-VF index and COPD prevalence. The relationship was verified by fitted smooth curves, generalized additive models, threshold effect analyses, subgroup analyses, and sensitivity analyses. RESULTS: In total, 7,680 subjects were recruited for the study, including 772 self-reported having COPD. The METS-VF index was positively related to COPD prevalence when adjusted for all covariates. The METS-VF index was classified by quartiles, and participants who scored highest on METS-VF were at a greater risk of COPD than those who scored lowest. According to a threshold effect analysis, the METS-VF index was negatively correlated with COPD prevalence with a METS-VF index <7.00, without statistical significance. Once the METS-VF index exceeded 7.00, there was a robust positive correlation between the METS-VF index and COPD prevalence. In the analysis of subgroups, the METS-VF index was positively correlated with COPD prevalence among subjects who were male, aged 40-59, and without asthma or hypertension. The results were robust in sensitivity analyses. METS-VF showed a significantly better diagnostic value for COPD than Body Mass Index (BMI). CONCLUSIONS: The METS-VF index has a non-linear and positive correlation with COPD prevalence in the middle-aged and elderly American population.


Subject(s)
Intra-Abdominal Fat , Nutrition Surveys , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/diagnosis , Middle Aged , Male , Intra-Abdominal Fat/metabolism , Female , Aged , United States/epidemiology , Prevalence , Metabolic Syndrome/epidemiology , Metabolic Syndrome/metabolism , Metabolic Syndrome/diagnosis
18.
Zhonghua Er Ke Za Zhi ; 62(9): 841-846, 2024 Sep 02.
Article in Chinese | MEDLINE | ID: mdl-39192441

ABSTRACT

Objective: To investigate the factors affecting the time taken for B cell reconstitution after rituximab (RTX) treatment in children with steroid-sensitive nephrotic syndrome. Methods: This was a retrospective cohort study. The clinical data of 42 children with SSNS who received treatment with RTX in Department of Nephrology, Rheumatology and Immunology, Children's Hospital Affiliated to Zhengzhou University between December 2019 and May 2023 were analyzed retrospectively. The data of demographics, immunosuppressant treatment and laboratory tests such as CD19+B cell count, urinary protein quantification were collected. The patients were divided into 2 groups, the early B cell reconstruction group and the late reconstruction group based on the average time of B cell reconstruction. A multivariate logistic regression model was used to analyze the factors impacting the timing of B cell reconstruction, and the predictive value of these factors was assessed by plotting the receiver operating characteristic (ROC) curve. Results: There were 42 children, with 35 males and 7 females. They were aged 3.5 (2.2, 5.9) years at the onset of PNS and (8.4±3.3) years at their first RTX treatment. The time for B cell reconstitution was (152±53) d. There were 20 children in the early reconstruction group and 22 children in the late reconstruction group. There were no statistically significant differences (all P>0.05) between the 2 groups in terms of the cumulative dose of steroids within 1 year before receiving RTX infusion (0.29 (0.16, 0.50) vs. 0.29 (0.19, 0.46) mg/(kg·d)), the percentage of children using tacrolimus before RTX (65%(13/20) vs. 45%(10/22)) and cumulative doses (0.04 (0.03, 0.05) vs. 0.03 (0.03, 0.06) mg/(kg·d)), the steroid doses at the time of RTX infusion (0.73 (0.49, 0.90) vs. 0.71 (0.58, 0.89) mg/(kg·d)), the percentage of children using tacrolimus at the initial RTX infusion (50% (10/20)vs. 41% (9/22)) and the doses (0.03 (0.02, 0.04) vs. 0.02 (0.01, 0.04) mg/(kg·d)), the discontinuation time of tacrolimus post-RTX infusion (71 (42, 91) vs. 64 (42, 91) d). A multivariate analysis revealed a correlation (OR=0.26, 95%CI 0.10-0.68, P=0.006) between B cell count following the second RTX infusion and the time taken for B cell reconstruction. The area under the ROC curve for B cell count after the RTX infusion in predicting the time to B cell reconstruction was 0.89 (95%CI 0.78-0.99, P<0.001) and the cut-off value was 0.925×106/L. Conclusions: The time of B cell reconstruction is not influenced by the previous or concurrent use of tacrolimus, regardless of its duration and the dosage of steroid and tacrolimus prior to the RTX infusion. Insteadly, the peripheral blood B cell count (0.925×106/L) following the second RTX infusion for SSNS is identified as an independent predictor of reconstruction time, allowing for a more precise prediction and early intervention to maintain disease remission.


Subject(s)
B-Lymphocytes , Nephrotic Syndrome , Rituximab , Humans , Rituximab/therapeutic use , Rituximab/administration & dosage , Female , Male , Nephrotic Syndrome/drug therapy , Retrospective Studies , Child , B-Lymphocytes/immunology , Child, Preschool , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/administration & dosage , Antigens, CD19 , Time Factors
19.
Nat Commun ; 15(1): 6782, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39117648

ABSTRACT

Intermetallic alloys have traditionally been characterized by their inherent brittleness due to their lack of sufficient slip systems and absence of strain hardening. However, here we developed a single-phase B2 high-entropy intermetallic alloy that is both strong and plastic. Unlike conventional intermetallics, this high-entropy alloy features a highly distorted crystalline lattice with complex chemical order, leading to multiple slip systems and high flow stress. In addition, the alloy exhibits a dynamic hardening mechanism triggered by dislocation gliding that preserves its strength across a wide range of temperatures. As a result, this high-entropy intermetallic circumvents precipitous thermal softening, with extensive plastic flows even at high homologous temperatures, outperforming a variety of both body-centered cubic and B2 alloys. These findings reveal a promising direction for the development of intermetallic alloys with broad engineering applications.

20.
Ultrasound Obstet Gynecol ; 64(3): 330-338, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39031515

ABSTRACT

OBJECTIVE: To investigate the trimester-specific associations between maternal total physical activity level vs moderate-to-vigorous exercise and fetal growth disorders. METHODS: We analyzed 2062 mother-neonate pairs participating in the longitudinal China Medical University Birth Cohort Study. The Pregnancy Physical Activity Questionnaire was used to assess the physical activity level of women during the three trimesters. A higher level of total physical activity was defined as meeting or exceeding the cohort-specific 75th percentile, and a higher level of exercise was defined according to the Physical Activity Guidelines for Americans. Fetal growth disorder was defined as small-for-gestational age (SGA) or large-for-gestational age (LGA) at birth. RESULTS: Of the neonates included in this study, 7.1% were SGA and 15.5% were LGA. A higher level of total physical activity during the first trimester (adjusted relative risk (aRR), 0.62 (95% CI, 0.42-0.91)) and second trimester (aRR, 0.62 (95% CI, 0.41-0.95)) was associated with a lower risk of SGA, and a higher level of total physical activity during the third trimester was associated with a lower risk of LGA (aRR, 0.73 (95% CI, 0.54-0.97)). When analyzing physical activity by subtype, a higher level of occupational physical activity during the first and second trimesters was associated negatively with SGA risk, and higher levels of occupational and low-intensity physical activity during the first trimester were associated negatively with LGA risk. No significant association was found between maternal adherence to the Physical Activity Guidelines for Americans and risk of fetal growth disorders. CONCLUSIONS: A higher total physical activity level during the first and second trimesters was associated with a decreased risk of SGA, whereas a higher total physical activity level in the third trimester was associated with a decreased risk of LGA. Pregnant women should be advised to increase their total physical activity levels instead of focusing on engaging in only moderate-to-vigorous exercise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Exercise , Fetal Development , Fetal Growth Retardation , Infant, Small for Gestational Age , Pregnancy Trimesters , Humans , Female , Pregnancy , Exercise/physiology , Adult , Pregnancy Trimesters/physiology , China , Fetal Development/physiology , Infant, Newborn , Longitudinal Studies , Surveys and Questionnaires , Fetal Macrosomia
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