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1.
Org Lett ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832831

ABSTRACT

Described herein is an efficient copper-catalyzed tandem alkyne indolylcupration-initiated 1,2-indole migration/6π-electrocyclic reaction of allene-ynamides with indoles by the in situ-generated metal carbenes. This method allows the efficient synthesis of valuable indole-fused spirobenzo[f]indole-cyclohexanes with high regio- and stereoselectivity. In addition, this reaction affords rapid access to the functionalized spirobenzo[f]indole-cyclohexanes in the absence of indoles by a presumable 5-exo-dig cyclization/Friedel-Crafts alkylation via copper-containing all-carbon 1,4-dipoles.

2.
Redox Biol ; 73: 103139, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38696898

ABSTRACT

In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia and in human coronary artery disease by analyzing metabolic profiles. We found that HHcy worsening is most sensitive to other metabolic disorders. To identify metabolic genes and metabolites responsible for the worsening metabolic crosstalk, we examined mRNA levels of 324 metabolic genes in Hcy, glucose-related and lipid metabolic systems. We examined Hcy-metabolites (Hcy, SAH and SAM) by LS-ESI-MS/MS in 6 organs (heart, liver, brain, lung, spleen, and kidney) from C57BL/6J mice. Through linear regression analysis of Hcy-metabolites and metabolic gene mRNA levels, we discovered that SAH-responsive genes were responsible for most metabolic changes and all metabolic crosstalk mediated by Serine, Taurine, and G3P. SAH-responsive genes worsen glucose metabolism and cause upper glycolysis activation and lower glycolysis suppression, indicative of the accumulation of glucose/glycogen and G3P, Serine synthesis inhibition, and ATP depletion. Insufficient Serine due to negative correlation of PHGDH with SAH concentration may inhibit the folate cycle and transsulfurarion pathway and consequential reduced antioxidant power, including glutathione, taurine, NADPH, and NAD+. Additionally, we identified SAH-activated pathological TG loop as the consequence of increased fatty acid (FA) uptake, FA ß-oxidation and Ac-CoA production along with lysosomal damage. We concluded that HHcy is most responsive to other metabolic changes in concomitant metabolic disorders and mediates worsening metabolic crosstalk mainly via SAH-responsive genes, that organ-specific Hcy metabolism determines organ-specific worsening metabolic reprogramming, and that SAH, acetyl-CoA, Serine and Taurine are critical metabolites mediating worsening metabolic crosstalk, redox disturbance, hypomethylation and hyperacetylation linking worsening metabolic reprogramming in metabolic syndrome.

3.
J Cancer Res Clin Oncol ; 150(5): 280, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802664

ABSTRACT

PROPOSE: To evaluate the advantage of the manual adaptive plans comparing to the scheduled plans, and explored clinical factors predicting patients suitable for adaptive strategy. METHODS AND MATERIALS: Eighty two patients with weekly online cone-beam computed tomography (CBCT) were enrolled. The re-CT simulation was performed after 15 fractions and a manual adaptive plan was developed if a significant deviation of the planning target volume (PTV) was found. To evaluate the dosimetric benefit, D98, homogeneity index (HI) and conformity index (CI) for the planning target volume (PTV), as well as D2cc of the bowel, bladder, sigmoid and rectum were compared between manual adaptive plans and scheduled ones. The clinical factors influencing target motion during radiotherapy were analyzed by chi-square test and logistic regression analysis. RESULTS: The CI and HI of the manual adaptive plans were significantly superior to the scheduled ones (P = 0.0002, 0.003, respectively), demonstrating a better dose coverage of the target volume. Compared to the scheduled plans, D98 of the manual adaptive plans increased by 3.3% (P = 0.0002), the average of D2cc to the rectum, bladder decreased 0.358 Gy (P = 0.000034) and 0.240 Gy (P = 0.03), respectively. In addition, the chi-square test demonstrated that age, primary tumor volume, and parametrial infiltration were the clinical factors influencing target motion during radiotherapy. Multivariate analysis further identified the large tumor volume (≥ 50cm3, OR = 3.254, P = 0.039) and parametrial infiltration (OR = 3.376, P = 0.018) as the independent risk factors. CONCLUSION: We found the most significant organ motion happened after 15 fractions during treatment. The manual adaptive plans improved the dose coverage and decreased the OAR doses. Patients with bulky mass or with parametrial infiltration were highly suggested to adaptive strategy during definitive radiotherapy due to the significant organ motion.


Subject(s)
Cone-Beam Computed Tomography , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Uterine Cervical Neoplasms , Humans , Female , Radiotherapy Planning, Computer-Assisted/methods , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/pathology , Middle Aged , Aged , Adult , Cone-Beam Computed Tomography/methods , Radiometry/methods , Organs at Risk/radiation effects , Aged, 80 and over
4.
Nat Genet ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811844

ABSTRACT

Genome-wide association studies of brain imaging phenotypes are mainly performed in European populations, but other populations are severely under-represented. Here, we conducted Chinese-alone and cross-ancestry genome-wide association studies of 3,414 brain imaging phenotypes in 7,058 Chinese Han and 33,224 white British participants. We identified 38 new associations in Chinese-alone analyses and 486 additional new associations in cross-ancestry meta-analyses at P < 1.46 × 10-11 for discovery and P < 0.05 for replication. We pooled significant autosomal associations identified by single- or cross-ancestry analyses into 6,443 independent associations, which showed uneven distribution in the genome and the phenotype subgroups. We further divided them into 44 associations with different effect sizes and 3,557 associations with similar effect sizes between ancestries. Loci of these associations were shared with 15 brain-related non-imaging traits including cognition and neuropsychiatric disorders. Our results provide a valuable catalog of genetic associations for brain imaging phenotypes in more diverse populations.

5.
Phytochemistry ; 223: 114119, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38705266

ABSTRACT

Six previously undescribed prenylated indole diketopiperazine alkaloids, talaromyines A-F (1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data including NMR, HR-ESI-MS, and electronic circular dichroism calculations, together with chemical analysis of hydrolysates. Compounds 1-5 represent the first example of spirocyclic indole diketopiperazines biosynthesized from the condensation of L-tryptophan and L-alanine. Compounds 2 and 4-5 showed selective inhibitory activities against phosphatases TCPTP and MEG2 with IC50 value of 17.9-29.7 µM, respectively. Compounds 4-5 exhibited mild cytotoxic activities against two human cancer cell lines H1975 and HepG-2.


Subject(s)
Diketopiperazines , Talaromyces , Talaromyces/chemistry , Diketopiperazines/chemistry , Diketopiperazines/pharmacology , Diketopiperazines/isolation & purification , Humans , Molecular Structure , Prenylation , Drug Screening Assays, Antitumor , Structure-Activity Relationship , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Indole Alkaloids/isolation & purification , Indole Alkaloids/chemistry , Indole Alkaloids/pharmacology , Alkaloids/chemistry , Alkaloids/pharmacology , Alkaloids/isolation & purification , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Hep G2 Cells , Cell Proliferation/drug effects , Phosphoric Monoester Hydrolases/antagonists & inhibitors , Phosphoric Monoester Hydrolases/metabolism , Cell Line, Tumor
6.
Eur J Radiol ; 176: 111514, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38776804

ABSTRACT

PURPOSE: To assess the utility of apparent diffusion coefficients (ADCs) of whole tumor volume (WTV) and functional tumor volume (FTV) in determining the pathologicalprognostic factors in epithelial ovarian cancers (EOCs). METHODS: A total of 155 consecutive patients who were diagnosed with EOC between January 2017 and August 2022 and underwent both conventional magnetic resonance imaging and diffusion-weighted imaging were assessed in this study. The maximum, minimum, and mean ADC values of the whole tumor (ADCwmax, ADCwmin, and ADCwmean, respectively) and functional tumor (ADCfmax, ADCfmin, and ADCfmean, respectively) as well as the WTV and FTV were derived from the ADC maps. The univariate and multivariate logistic regression analyses and receiver operating characteristic curve (ROC) analysis were used to assess the correlation between these ADC values and the pathological prognostic factors, namely subtypes, lymph node metastasis (LNM), Ki-67 index, and p53 expression. RESULTS: The ADCfmean value was significantly lower in type II EOC, LNM-positive, and high-Ki-67 index groups compared to the type I EOC, LNM-negative, and low-Ki-67 index groups (p ≤ 0.001). Similarly, the ADCwmean and ADCfmean values were lower in the mutant-p53 group compared to the wild-type-p53 group (p ≤ 0.001). Additionally, the ADCfmean showed the highest area under the ROC curve (AUC) for evaluating type II EOC (0.725), LNM-positive (0.782), and high-Ki-67 index (0.688) samples among the given ROC curves, while both ADCwmean and ADCfmean showed high AUCs for assessing p53 expression (0.694 and 0.678, respectively). CONCLUSION: The FTV-derived ADC values, especially ADCfmean, can be used to assess preoperative prognostic factors in EOCs.

7.
World J Gastrointest Oncol ; 16(5): 2253-2260, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38764812

ABSTRACT

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) is a rare malignant mesenchymal tumor with a poor prognosis. It mainly occurs in the extremities, trunk, head and neck, and retroperitoneum regions. Owing to the lack of specific clinical manifestations and imaging features, UPS diagnosis mainly depends on pathological and immunohistochemical examinations for exclusive diagnosis. Here we report an extremely rare case of high-grade UPS in the common bile duct (CBD). There are limited available data on such cases. CASE SUMMARY: A 70-year-old woman was admitted to our department with yellow eyes and urine accompanied by upper abdominal distending pain for 2 wk. Her laboratory data suggested significantly elevated hepatorenal function levels. The imaging data revealed calculous cholecystitis, intrahepatic and extrahepatic bile duct dilation with extrahepatic bile duct calculi, and a space-occupying lesion at the distal CBD. After endoscopic biliary stenting and symptomatic support therapy, CBD exploration and biopsy were performed. The frozen section indicated malignant spindle cell tumor of the CBD mass, and further radical pancreaticoduodenectomy was performed. Finally, the neoplasm was diagnosed as a high-grade UPS combined with the light-microscopic morphology and immunohistochemical results. CONCLUSION: This extremely rare case highlighted the need for increasing physicians' vigilance, reducing the odds of misdiagnosis, and providing appropriate treatment strategies.

8.
Front Psychol ; 15: 1343186, 2024.
Article in English | MEDLINE | ID: mdl-38659684

ABSTRACT

Background and aims: In China, a significant number of undergraduates are experiencing poor sleep quality. This study was designed to investigate the prevalence of poor sleep quality and identify associated factors among undergraduates in Jiangsu Province, China. Methods: A total of 8,457 participants were collected in 2022 using whole-group convenience sampling. The factors studied included basic demographics, family and social support, personal lifestyles, physical and mental health, mobile phone addiction index (MPAI), and the Connor-Davidson resilience scale (CD-RISC). The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Four models, including weighted multiple linear regression, binary logistic regression, weighted linear mixed model, and logistic regression with random effects, were applied to identify associated factors for sleep quality. Results: Of the 8,457 participants analyzed, 26.64% (2,253) were classified into the poor sleep quality group with a PSQI score >7. No significant relationship was found between sleep quality and gender, native place, economic level of family, physical exercise, dormitory light, dormitory hygiene, and amativeness matter. Risk factors for sleep quality identified by the four models included lower CD-RISC, higher MPAI, fourth grade or above, smoking, drinking, greater academic pressure, greater employment pressure, roommate sleeping late, noisy dormitory, poorer physical health status, poorer mental health status, and psychological counseling. Conclusions: These findings provide valuable insights for university administrators, enabling them to better understand the risk factors associated with poor sleep quality in undergraduates. By identifying these factors, administrators can provide targeted intervention measures and counseling programs to improve students' sleep quality.

9.
BMC Cardiovasc Disord ; 24(1): 230, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38678215

ABSTRACT

BACKGROUND: Unidentified heart failure occurs in patients with multiple myeloma when their heart was involved. CMR with late gadolinium enhancement (LGE) and T1 mapping can identify myocardial amyloid infiltrations. PURPOSE: To explore the role of CMR with late gadolinium enhancement (LGE) and T1 mapping for detection of multiple myeloma patients'heart. MATERIAL AND METHODS: A total of 16 MM patients with above underwent CMR (3.0-T) with T1 mapping (pre-contrast and post-contrast) and LGE imaging. In addition, 26 patients with non-obstructive hypertrophic cardiomyopathy and 26 healthy volunteers were compared to age- and sex-matched healthy controls without a history of cardiac disease, diabetes mellitus, or normal in CMR. All statistical analyses were performed using the statistical software GraphPad Prism. The measurement data were represented by median (X) and single sample T test was adopted. Enumeration data were represented by examples and Chi-tested was adopted. All tests were two-sided, and P values < 0.05 were considered statistically significant. RESULTS: In MM group, LVEF was lower than healthy controls and higher than that of non-obstructive hypertrophic cardiomyopathy group, but without statistically significant difference (%: 49.1 ± 17.5 vs. 55.6 ± 10.3, 40.4 ± 15.6, all P > 0.05). Pre-contrast T1 values of MM group were obviously higher than those of healthy controls and non-obstructive hypertrophic cardiomyopathy group (ms:1462.0 ± 71.3vs. 1269.3 ± 42.3, 1324.0 ± 45.1, all P < 0.05). 16 cases (100%) in MM group all had LGE. CONCLUSION: LGE joint T1 mapping wider clinical use techniques and follow-up the patients'disease severity.


Subject(s)
Cardiomyopathy, Hypertrophic , Contrast Media , Magnetic Resonance Imaging, Cine , Multiple Myeloma , Predictive Value of Tests , Stroke Volume , Ventricular Function, Left , Humans , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/diagnosis , Male , Female , Middle Aged , Contrast Media/administration & dosage , Aged , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/physiopathology , Case-Control Studies , Myocardium/pathology , Adult , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Heart Failure/diagnosis , Heart Failure/etiology
10.
Bioresour Bioprocess ; 11(1): 2, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38647587

ABSTRACT

Perylenequinones (PQs) from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy. However, the lower yield of PQ production in mycelium cultures is an important bottleneck for their clinical application. Light has long been recognized as a pivotal regulatory signal for fungal secondary metabolite biosynthesis. In this study, we explored the role of nitric oxide (NO) in the growth and PQ biosynthesis in mycelium cultures of Shiraia sp. S9 exposed to red light. The continuous irradiation with red light (627 nm, 200 lx) suppressed fungal conidiation, promoted hyphal branching, and elicited a notable increase in PQ accumulation. Red light exposure induced NO generation, peaking to 81.7 µmol/g FW on day 8 of the culture, with the involvement of nitric oxide synthase (NOS)- or nitrate reductase (NR)-dependent pathways. The application of a NO donor sodium nitroprusside (SNP) restored conidiation of Shiraia sp. S9 under red light and stimulated PQ production, which was mitigated upon the introduction of NO scavenger carboxy-PTIO or soluble guanylate cyclase inhibitor NS-2028. These results showed that red light-induced NO, as a signaling molecule, was involved in the regulation of growth and PQ production in Shiraia sp. S9 through the NO-cGMP-PKG signaling pathway. While mycelial H2O2 content exhibited no significant alternations, a transient increase of intracellular Ca2+ and extracellular ATP (eATP) content was detected upon exposure to red light. The generation of NO was found to be interdependent on cytosolic Ca2+ and eATP concentration. These signal molecules cooperated synergistically to enhance membrane permeability and elevate the transcript levels of PQ biosynthetic genes in Shiraia sp. S9. Notably, the combined treatment of red light with 5 µM SNP yielded a synergistic effect, resulting in a substantially higher level of hypocrellin A (HA, 254 mg/L), about 3.0-fold over the dark control. Our findings provide valuable insights into the regulation of NO on fungal secondary metabolite biosynthesis and present a promising strategy involving the combined elicitation with SNP for enhanced production of photoactive PQs and other valuable secondary metabolites in fungi.

11.
Org Lett ; 26(18): 3715-3721, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38678545

ABSTRACT

A highly convenient copper(I)-catalyzed oxidation-initiated cyclopropanation of indolyl ynamide for the rapid construction of indole-fused cyclopropane-lactams is described, which represents, to the best of our knowledge, the first non-noble-metal-catalyzed indolyl ynamide oxidation/dearomatization by the in situ generated α-oxo copper carbenes. Compared to hydrazone and diazo, the use of alkynes as carbene precursors allows cyclopropanation to occur under a safe and convenient pathway. Moreover, this transformation can lead to the divergent synthesis of pentacyclic spiroindolines involving the reversal of ynamide regioselectivity by engineering substrate structures.

12.
Br J Radiol ; 97(1158): 1139-1145, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38662891

ABSTRACT

OBJECTIVE: This study aimed to explore the value of apparent diffusion coefficient (ADC) histogram based on whole lesion volume in distinguishing stage IA endometrial carcinoma from the endometrial polyp. METHODS: MRI of 108 patients with endometrial lesions confirmed by pathology were retrospectively analysed, including 65 cases of stage IA endometrial carcinoma and 43 cases of endometrial polyp. The volumetric ADC histogram metrics and general imaging features were evaluated and measured simultaneously. All the features were compared between the 2 groups. The receiver operating characteristic curve was utilized to evaluate the diagnostic performance. RESULTS: The mean, max, min, and percentiles (10th, 25th, 50th, 75th, 95th) ADC values of endometrial carcinoma were significantly lower than that of polyp (all P < .05). The skewness and kurtosis of ADC values in the endometrial carcinoma group were significantly higher than those in the endometrial polyp group, and the variance of ADC values in the endometrial carcinoma group was lower than those in the endometrial polyp group (all P < .05). Endometrial carcinoma demonstrated more obvious myometrial invasion combined with intralesion haemorrhage than polyp (all P < .05). The 25th percentile of ADC values achieved the largest areas under the curve (0.861) among all the ADC histogram metrics and general imaging features, and the sensitivity and specificity were 83.08% and 76.74%, with the cut-off value of 1.01 × 10-3 mm2/s. CONCLUSION: The volumetric ADC histogram analysis was an effective method in differentiating endometrial carcinoma from an endometrial polyp. The 25th percentile of ADC values has satisfactory performance for detecting malignancy in the endometrium. ADVANCES IN KNOWLEDGE: The ADC histogram metric based on whole lesion is a promising imaging-maker in differentiating endometrial benign and malignant lesions.


Subject(s)
Diffusion Magnetic Resonance Imaging , Endometrial Neoplasms , Polyps , Humans , Female , Endometrial Neoplasms/diagnostic imaging , Endometrial Neoplasms/pathology , Polyps/diagnostic imaging , Polyps/pathology , Middle Aged , Retrospective Studies , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging/methods , Aged , Adult , Sensitivity and Specificity , Neoplasm Staging , Endometrium/diagnostic imaging , Endometrium/pathology , ROC Curve
13.
J Nat Prod ; 87(4): 810-819, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38427823

ABSTRACT

Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.


Subject(s)
Alkaloids , Anti-Bacterial Agents , Microbial Sensitivity Tests , Alkaloids/pharmacology , Alkaloids/chemistry , Alkaloids/isolation & purification , Molecular Structure , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Structure-Activity Relationship , Marine Biology , Ascomycota/chemistry , Fluorenes/pharmacology , Fluorenes/chemistry , Fluorenes/isolation & purification , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors
14.
Huan Jing Ke Xue ; 45(3): 1392-1401, 2024 Mar 08.
Article in Chinese | MEDLINE | ID: mdl-38471855

ABSTRACT

This study investigated the concentrations of atmospheric pollutants in the urban area of Suzhou from May to June, 2017-2021. The variation characteristics and annual changes of ozone (O3), nitrogen oxide (NOx), total oxidant (Ox), carbon monoxide (CO), and volatile organic compounds (VOCs) were analyzed. The O3 formation mechanism and its annual changes were studied using an Observation-Based Model (OBM), and VOCs source apportionments and their trends were discussed. The results indicated that ① The volume fractions of Ox and the concentrations of NOx and CO have decreased in the urban area of Suzhou in recent years, while the volume fractions of VOCs have increased, and sufficient photochemical conditions for O3 formation still existed during polluted days. ② The O3-NOx-VOCs sensitivity in Suzhou was in the VOCs-limited regime. The long-term reduction ratio between VOCs and NOx should not be less than 5:1, and aromatics and alkenes were the critical VOCs for mitigating O3 pollution. ③ The results of VOCs source apportionment revealed that industrial emissions, gasoline vehicle exhaust, and diesel engine exhaust were the major sources of VOC emissions in Suzhou. Industrial emissions and solvent usage declined from 2017 to 2021; however, gasoline vehicle exhaust and gasoline evaporation, which possess higher O3 formation potential(OFP), increased significantly. ④ The OFP source apportionments results indicated that controlling VOC emissions from solvent usage and gasoline vehicle exhaust is crucial for O3 pollution control in Suzhou.

15.
Vitam Horm ; 124: 1-37, 2024.
Article in English | MEDLINE | ID: mdl-38408797

ABSTRACT

Steroid hormones are derived from a common precursor molecule, cholesterol, and regulate a wide range of physiologic function including reproduction, salt balance, maintenance of secondary sexual characteristics, response to stress, neuronal function, and various metabolic processes. Among the steroids synthesized by the adrenal and gonadal tissues, adrenal mineralocorticoids, and glucocorticoids are essential for life. The process of steroidogenesis is regulated at multiple levels largely by transcriptional, posttranscriptional, translational, and posttranslational regulation of the steroidogenic enzymes (i.e., cytochrome P450s and hydroxysteroid dehydrogenases), cellular compartmentalization of the steroidogenic enzymes, and cholesterol processing and transport proteins. In recent years, small noncoding RNAs, termed microRNAs (miRNAs) have been recognized as major post-transcriptional regulators of gene expression with essential roles in numerous biological processes and disease pathologies. Although their role in the regulation of steroidogenesis is still emerging, several recent studies have contributed significantly to our understanding of the role miRNAs play in the regulation of the steroidogenic process. This chapter focuses on the recent developments in miRNA regulation of adrenal glucocorticoid and androgen production in humans and rodents.


Subject(s)
MicroRNAs , Humans , MicroRNAs/genetics , Glucocorticoids , Androgens , Steroids/metabolism , Cholesterol/metabolism
16.
Curr Med Imaging ; 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38415457

ABSTRACT

AIM: To identify age-matched healthy volunteers, non-cirrhotic chronic liver disease (CLD) and cirrhotic patients based on portal hemodynamic parameters using 4D flow MRI. METHODS: A total of 10 age-matched healthy volunteers and 69 CLD patients were enrolled and underwent 4D flow MRI prospectively. 4D flow MR images were processed by an MD in biomedical engineering working on the GTFlow platform. Portal hemodynamic parameters include net flow (mL/cycle), flow volume per second through the lumen (mL/sec), average flow velocity (cm/sec), and maximum flow velocity (cm/sec). The difference in portal hemodynamic parameters of 4D flow MRI was compared among healthy volunteers, non-cirrhotic CLD patients and patients with cirrhosis by one-way ANOVA or Kruskal-Wallis nonparametric test and post hoc tests. RESULTS: 10 CLD patients without cirrhosis and 56 patients with cirrhosis were eventually included, along with 10 healthy volunteers who were divided into three groups. 3 patients with cirrhosis whose image quality did not meet the requirements were excluded. There were no significant differences in portal hemodynamic parameters among the three groups except portal average velocity (P > 0.05). There was no statistical difference in all portal hemodynamic parameters of 4D flow MRI between healthy volunteers and patients with cirrhosis (P > 0.05). There were significant differences in portal average velocity between non-cirrhotic CLD patients, healthy volunteers and patients with cirrhosis, respectively (11.44±3.93 vs 8.10±2.66, P=0.013; 11.44±3.93 vs 8.60±2.22, P=0.007). CONCLUSION: Portal average velocity obtained by 4D flow MRI can be an auxiliary means to identify cirrhosis in patients with CLD.

17.
Cell Rep ; 43(2): 113726, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38308844

ABSTRACT

Warm ambient conditions induce thermomorphogenesis and affect plant growth and development. However, the chromatin regulatory mechanisms involved in thermomorphogenesis remain largely obscure. In this study, we show that the histone methylation readers MORF-related gene 1 and 2 (MRG1/2) are required to promote hypocotyl elongation in response to warm ambient conditions. A transcriptome sequencing analysis indicates that MRG1/2 and phytochrome interacting factor 4 (PIF4) coactivate a number of thermoresponsive genes, including YUCCA8, which encodes a rate-limiting enzyme in the auxin biosynthesis pathway. Additionally, MRG2 physically interacts with PIF4 to bind to thermoresponsive genes and enhances the H4K5 acetylation of the chromatin of target genes in a PIF4-dependent manner. Furthermore, MRG2 competes with phyB for binding to PIF4 and stabilizes PIF4 in planta. Our study indicates that MRG1/2 activate thermoresponsive genes by inducing histone acetylation and stabilizing PIF4 in Arabidopsis.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Phytochrome , Histones , Vernalization , Arabidopsis/genetics , Chromatin , Methylation , Arabidopsis Proteins/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , Chromosomal Proteins, Non-Histone
18.
J Magn Reson Imaging ; 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38299767

ABSTRACT

BACKGROUND: Serum creatinine (Scr) may be not suited to timely and accurately reflect kidney injury related to chronic liver disease. Currently, the ability of arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) sequences to evaluate renal blood flow (RBF) and blood oxygen in chronic liver disease remains to be verified. PURPOSE: To investigate the value of ASL and BOLD imaging in evaluating hemodynamics and oxygenation changes during kidney injury in an animal model of chronic liver disease. STUDY TYPE: Prospective. ANIMAL MODEL: Chronic liver disease model was established by subcutaneous injection of carbon tetrachloride. Forty-three male Sprague-Dawley rats (8 weeks) were divided into a pathological group (0, 2, 4, 6, 8, 12 weeks, each group: N = 6) and a continuous-scanning group (N = 7). FIELD STRENGTH/SEQUENCE: 3-T, ASL, BOLD, and T2W. ASSESSMENT: Regions of interest in the cortex (CO), outer stripe of the outer medulla (OSOM), and inner stripe of the outer medulla (ISOM) are manually delineated. The RBF and T2* values at each time point (0, 2, 4, 6, 8, 12 weeks) are measured and compared. Hematoxylin-eosin score (HE Score, damage area scoring method), alpha-smooth muscle actin (α-SMA), hypoxia-inducible factor-1alpha (HIF-1α), peritubular capillar (PTC) density, Scr, and neutrophil gelatinase-associated lipocalin were harvested. STATISTICAL TESTS: Analysis of variance, Spearman correlation analysis, Kruskal-Wallis tests, and receiver operating characteristic analysis with the area under the curve (AUC). A P-value <0.05 was considered statistically significant. RESULTS: Renal RBF and T2* values of CO, OSOM, and ISOM were significantly different from baseline. Both RBF and T2* were significantly correlated with HE Score, α-SMA, HIF-1α, and PTC density (|r| = 0.406-0.853). RBF demonstrated superior diagnostic capability in identifying severe kidney injury in this model of chronic liver disease (AUC = 0.964). DATA CONCLUSION: Imaging by ASL and BOLD may detect renal hemodynamics and oxygenation changes related to chronic liver disease early. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

19.
IEEE Trans Pattern Anal Mach Intell ; 46(5): 3290-3304, 2024 May.
Article in English | MEDLINE | ID: mdl-38190688

ABSTRACT

This study proposes a set of generic rules to revise existing neural networks for 3D point cloud processing to rotation-equivariant quaternion neural networks (REQNNs), in order to make feature representations of neural networks to be rotation-equivariant and permutation-invariant. Rotation equivariance of features means that the feature computed on a rotated input point cloud is the same as applying the same rotation transformation to the feature computed on the original input point cloud. We find that the rotation-equivariance of features is naturally satisfied, if a neural network uses quaternion features. Interestingly, we prove that such a network revision also makes gradients of features in the REQNN to be rotation-equivariant w.r.t. inputs, and the training of the REQNN to be rotation-invariant w.r.t. inputs. Besides, permutation-invariance examines whether the intermediate-layer features are invariant, when we reorder input points. We also evaluate the stability of knowledge representations of REQNNs, and the robustness of REQNNs to adversarial rotation attacks. Experiments have shown that REQNNs outperform traditional neural networks in both terms of classification accuracy and robustness on rotated testing samples.

20.
Death Stud ; 48(6): 630-639, 2024.
Article in English | MEDLINE | ID: mdl-38236991

ABSTRACT

This cohort study investigated factors associated with 336 Taiwanese family caregivers' emotional and cognitive preparedness for death of a loved one with terminal cancer. Caregivers' death-preparedness states (no-death-preparedness [as reference], cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) were previously identified. Associations of factors with these states were determined by a hierarchical generalized linear model. Financial hardship decreased caregivers' likelihood for the emotional-death-preparedness-only and sufficient-death-preparedness states. Physician prognostic disclosure increased membership in the cognitive-death-preparedness-only and sufficient-death-preparedness states. The better the quality of the patient-caregiver relationship, the higher the odds for the emotional-death-preparedness-only and sufficient-death-preparedness states, whereas the greater the tendency for caregivers to communicate end-of-life issues with their loved one, the lower the odds for emotional-death-preparedness-only state membership. Stronger coping capacity increased membership in the emotional-death-preparedness-only state, but perceived social support was not associated with state membership. Providing effective interventions tailored to at-risk family caregivers' specific needs may facilitate their death preparedness.


Subject(s)
Adaptation, Psychological , Caregivers , Neoplasms , Humans , Caregivers/psychology , Taiwan , Male , Neoplasms/psychology , Female , Middle Aged , Adult , Attitude to Death , Social Support , Aged , Cohort Studies , Family/psychology
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