T1 mapping combined with arterial spin labeling MRI to identify renal injury in patients with liver cirrhosis.

Purpose: We investigated the capability and imaging criteria of T1 mapping and arterial spin labeling (ASL) MRI to identify renal injury in patients with liver cirrhosis. Methods: We recruited 27 patients with cirrhosis and normal renal function (cirrhosis-NR), 10 with cirrhosis and renal dysfunction (cirrhosis-RD) and 23 normal controls (NCs). All participants were examined via renal T1 mapping and ASL imaging. Renal blood flow (RBF) derived from ASL was measured from the renal cortex, and T1 values were measured from the renal parenchyma (cortex and medulla). MRI parameters were compared between groups. Diagnostic performances for detecting renal impairment were statistically analyzed. Results: Cortical T1 (cT1) and medullary T1 (mT1) were significantly lower in the NCs than in the cirrhosis-NR group. The cortical RBF showed no significant changes between the NCs and cirrhosis-NR group but was markedly decreased in the cirrhosis-RD group. The areas under the curve (AUCs) for discriminating cirrhosis-NR from NCs were 0.883 and 0.826 by cT1 and mT1, respectively. Cortical RBF identified cirrhosis-RD with AUC of 0.978, and correlated with serum creatinine (r = -0.334) and the estimated glomerular filtration rate (r = 0.483). A classification and regression tree based on cortical RBF and cT1 achieved 85% accuracy in detecting renal impairment in the cirrhosis. Conclusion: Renal T1 values might be sensitive predictors of early renal impairment in patients with cirrhosis-NR. RBF enabled quantifying renal perfusion impairment in patients with cirrhosis-RD. The diagnostic algorithm based on cortical RBF and T1 values allowed detecting renal injury during cirrhosis.

[Molecular mechanism of CDO1 regulating common metabolic diseases].

Cysteine dioxygenase type 1 (CDO1) belongs to the cysteine dioxygenase (CDO) family. CDO1 is the key enzyme in cysteine catabolism and taurine synthesis. CDO1 is highly expressed in liver, adipose tissue, pancreas, kidney, lung, brain and small intestine. CDO1 is involved in the pathophysiological regulation of various common metabolic diseases, such as lipid metabolism disorders, insulin resistance, obesity, tumors/cancers, and neurodegenerative diseases. This article summarizes the research progress on the molecular mechanisms of CDO1 regulation of common metabolic diseases in recent years, aiming to provide new theoretical and practical basis for CDO1-targeted therapy for insulin resistance, obesity, tumors/cancers, and neurodegenerative diseases.

Cord blood vitamin A and vitamin D levels in relation to physical growth in exclusively breastfed infants aged 0-6 months.

Background: Vitamins A and D are essential for the health of pregnant women and infants. Nevertheless, the relationship between umbilical cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants remains uncertain. Objective: This cohort study aims to examine the relationship between cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants aged 0-6 months. Methods: 140 singleton mother-infant pairs were recruited in total. Questionnaires were used to collect maternal and infant information, and liquid chromatography was utilized to quantify the levels of vitamins A and D in the umbilical cord blood. Anthropometric measurements were conducted at birth, at 3 and 6 months of age, and the weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HAZ), and BMI-for-age z-score (BMIZ) were calculated. Univariate and multivariate linear regression models were used for the analysis. Results: The average concentration of vitamins A and D in cord blood was 0.58 ± 0.20 µmol/L and 34.07 ± 13.35 nmol/L, both below the normal range for children. After adjusting for confounding factors, vitamin A levels in cord blood positively correlated with HAZ growth in infants aged 3-6 months (ß= 0.75, P < 0.01) while vitamin D levels negatively correlated with LAZ growth (ß= -0.01, P = 0.01) and positively correlated with BMIZ growth (ß= 0.02, P < 0.01). Conclusion: Higher Vitamin A levels at birth promote HAZ growth in infants aged 3-6 months while higher vitamin D levels at birth promote BMIZ growth in infants aged 3-6 months. Clinical trial registration: https://register.clinicaltrials.gov, identifier NCT04017286.

RNA-binding protein AZGP1 inhibits epithelial cell proliferation by regulating the genes of alternative splicing in COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity, disability, and mortality rates worldwide. RNA-binding proteins (RBPs) might regulate genes involved in oxidative stress and inflammation in COPD patients. Single-cell transcriptome sequencing (scRNA-seq) offers an accurate tool for identifying intercellular heterogeneity and the diversity of immune cells. However, the role of RBPs in the regulation of various cells, especially AT2 cells, remains elusive. MATERIALS AND METHODS: A scRNA-seq dataset (GSE173896) and a bulk RNA-seq dataset acquired from airway tissues (GSE124180) were employed for data mining. Next, RNA-seq analysis was performed in both COPD and control patients. Differentially expressed genes (DEGs) were identified using criteria of fold change (FC ≥ 1.5 or ≤ 1.5) and P value ≤ 0.05. Lastly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and alternative splicing identification analyses were carried out. RESULTS: RBP genes exhibited specific expression patterns across different cell groups and participated in cell proliferation and mitochondrial dysfunction in AT2 cells. As an RBP, AZGP1 expression was upregulated in both the scRNA-seq and RNA-seq datasets. It might potentially be a candidate immune biomarker that regulates COPD progression by modulating AT2 cell proliferation and adhesion by regulating the expression of SAMD5, DNER, DPYSL3, GBP5, GBP3, and KCNJ2. Moreover, AZGP1 regulated alternative splicing events in COPD, particularly DDAH1 and SFRP1, holding significant implications in COPD. CONCLUSION: RBP gene AZGP1 inhibits epithelial cell proliferation by regulating genes participating in alternative splicing in COPD.

Multi-parametric MRI-based machine learning model for prediction of pathological grade of renal injury in a rat kidney cold ischemia-reperfusion injury model.

BACKGROUND: Renal cold ischemia-reperfusion injury (CIRI), a pathological process during kidney transplantation, may result in delayed graft function and negatively impact graft survival and function. There is a lack of an accurate and non-invasive tool for evaluating the degree of CIRI. Multi-parametric MRI has been widely used to detect and evaluate kidney injury. The machine learning algorithms introduced the opportunity to combine biomarkers from different MRI metrics into a single classifier. OBJECTIVE: To evaluate the performance of multi-parametric magnetic resonance imaging for grading renal injury in a rat model of renal cold ischemia-reperfusion injury using a machine learning approach. METHODS: Eighty male SD rats were selected to establish a renal cold ischemia -reperfusion model, and all performed multiparametric MRI scans (DWI, IVIM, DKI, BOLD, T1mapping and ASL), followed by pathological analysis. A total of 25 parameters of renal cortex and medulla were analyzed as features. The pathology scores were divided into 3 groups using K-means clustering method. Lasso regression was applied for the initial selecting of features. The optimal features and the best techniques for pathological grading were obtained. Multiple classifiers were used to construct models to evaluate the predictive value for pathology grading. RESULTS: All rats were categorized into mild, moderate, and severe injury group according the pathologic scores. The 8 features that correlated better with the pathologic classification were medullary and cortical Dp, cortical T2*, cortical Fp, medullary T2*, ∆T1, cortical RBF, medullary T1. The accuracy(0.83, 0.850, 0.81, respectively) and AUC (0.95, 0.93, 0.90, respectively) for pathologic classification of the logistic regression, SVM, and RF are significantly higher than other classifiers. For the logistic model and combining logistic, RF and SVM model of different techniques for pathology grading, the stable and perform are both well. Based on logistic regression, IVIM has the highest AUC (0.93) for pathological grading, followed by BOLD(0.90). CONCLUSION: The multi-parametric MRI-based machine learning model could be valuable for noninvasive assessment of the degree of renal injury.

Analysis of metabolic characteristics of metabolic syndrome in elderly patients with gastric cancer by non-targeted metabolomics.

BACKGROUND: The relationship between metabolic syndrome (MetS) and gastric cancer (GC), which is a common metabolic disease, has attracted much attention. However, the specific metabolic characteristics of MetS in elderly patients with GC remain unclear. AIM: To investigate the differentially abundant metabolites and metabolic pathways between preoperative frailty and MetS in elderly patients with GC based on nontargeted metabolomics techniques. METHODS: In this study, 125 patients with nonfrail nonmeal GC were selected as the control group, and 50 patients with GC in the frail group were selected as the frail group. Sixty-five patients with GC combined with MetS alone were included in the MetS group, and 50 patients with GC combined with MetS were included in the MetS group. Nontargeted metabolomics techniques were used to measure plasma metabolite levels by ultrahigh-performance liquid chromatography-mass spectrometry. Multivariate statistical analysis was performed by principal component analysis, orthogonal partial least squares, pattern recognition analysis, cluster analysis, and metabolic pathway annotation. RESULTS: A total of 125 different metabolites, including amino acids, glycerophospholipids, sphingolipids, fatty acids, sugars, nucleosides and nucleotides, and acidic compounds, were identified via nontargeted metabolomics techniques. Compared with those in the control group, there were 41, 32, and 52 different metabolites in the MetS group, the debilitated group, and the combined group, respectively. Lipid metabolites were significantly increased in the MetS group. In the weak group, amino acids and most glycerol phospholipid metabolites decreased significantly, and fatty acids and sphingosine increased significantly. The combined group was characterized by significantly increased levels of nucleotide metabolites and acidic compounds. The alanine, aspartic acid, and glutamate metabolic pathways were obviously enriched in the asthenic group, and the glycerol and phospholipid metabolic pathways were obviously enriched in the combined group. CONCLUSION: Elderly GC patients with simple frailty, simple combined MetS, and frailty combined with MetS have different metabolic characteristics, among which amino acid and glycerophospholipid metabolite levels are significantly lower in frail elderly GC patients, and comprehensive supplementation of fat and protein should be considered. Many kinds of metabolites, such as amino acids, lipids, nucleotides, and acidic compounds, are abnormally abundant in patients with MetS combined with fthenia, which may be related to tumor-related metabolic disorders.

Copper-Catalyzed Directed Hydroindolation/Annulation Sequence of Alkynes with Indoles via Copper Carbenes.

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.

PLA tissue-engineered scaffolds loaded with sustained-release active substance chitosan nanoparticles: Modeling BSA-bFGF as the active substance.

The utilization of basic fibroblast growth factor (bFGF) in the development of tissue-engineered scaffolds is both challenging and imperative. In our pursuit of creating a scaffold that aligns with the natural healing process, we initially fabricated chitosan-bFGF nanoparticles (CS-bFGF NPs) through electrostatic spraying. Subsequently, polylactic acid (PLA) fiber was prepared using electrospinning technique, and the CS-bFGF NPs were uniformly embedded within the pores of porous PLA fibers. Scanning electron micrographs illustrate the smooth surface of the nanoparticles, showing a porous structure intricately attached to PLA fibers. Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) analyses provided conclusive evidence that the CS-bFGF NPs were uniformly distributed throughout the porous PLA fibers, forming a robust physical bond through electrostatic adsorption. The resultant scaffolds exhibited commendable mechanical properties and hydrophilicity, facilitating a sustained-release for 72 h. Furthermore, the biocompatibility and degradation performance of the scaffolds were substantiated by monitoring conductivity and pH changes in pure water over different time intervals, complemented by scanning electron microscopy (SEM) observations. Cell experiments confirmed the cytocompatibility of the scaffolds. In animal studies, the group treated with 16 % NPs/Scaffold demonstrated the highest epidermal reconstruction rate. In summary, our developed materials present a promising candidate for serving as a tissue engineering scaffold, showcasing exceptional biocompatibility, sustained-release characteristics, and substantial potential for promoting epidermal regeneration.

Use of Intravoxel Incoherent Motion Diffusion-Weighted Imaging to Assess Mesenchymal Stromal Cells Promoting Liver Regeneration in a Rat Model.

RATIONALE AND OBJECTIVES: Mesenchymal stem cells (MSCs) have the potential to promote liver regeneration, but the process is unclear. This study aims to explore the therapeutic effects and dynamic processes of MSCs in liver regeneration through intravoxel incoherent motion (IVIM) imaging. ANIMAL MODEL: 70 adult Sprague-Dawley rats were randomly divided into either the control or MSC group (n = 35/group). All rats received a partial hepatectomy (PH) with the left lateral and middle lobes removed. Each group was divided into seven subgroups: pre-PH and 1, 2, 3, 5, 7, and 14 days post-PH (n = 5 rats/subgroup). Magnetic resonance imaging (MRI) was performed before obtaining pathological specimens at each time point on postoperative days 1, 2, 3, 5, 7, and 14. The MRI parameters for the pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF) were calculated. Correlation analysis was conducted for the biochemical markers (alanine transaminase [ALT], aspartate transaminase [AST], and total bilirubin [TBIL]), histopathological findings (hepatocyte size and Ki-67 proliferation index), liver volume (LV) and liver regeneration rate (LLR). RESULTS: Liver D, D* , and PF differed significantly between the control and MSC groups at all time points (all P < 0.05). After PH, the D increased, then decreased, and the D* and PF decreased, then increased in both groups. The hepatocyte Ki-67 proliferation index of the MSC group was lower on day 2 post-PH, but higher on days 3 and 5 post-PH than that of the control group. Starting from day 3 post-PH, both the LV and LLR in the MSC group were greater than those in the control group (all P < 0.05). Hepatocytes were larger in the MSC group than in the control group on days 2 and 7 post-PH. In the MSC group, the D, D* , and PF were correlated with the AST levels, Ki-67 index and hepatocyte size (|r|=0.35-0.71; P < 0.05). In the control group, the D and D* were correlated with ALT levels, AST levels, Ki-67 index, LLR, LV, and hepatocyte size (|r|=0.34-0.95; P < 0.05). CONCLUSION: Bone marrow MSC therapy can promote hepatocyte hypertrophy and prolong liver proliferation post-PH. IVIM parameters allow non-invasively evaluating the efficacy of MSCs in promoting LR.

Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

Undifferentiated high-grade pleomorphic sarcoma of the common bile duct: A case report and review of literature.

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.

Prenylated indole diketopiperazine alkaloids as phosphatase inhibitors from the marine-derived fungus Talaromyces purpureogenus.

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.

The clinical practice and dosimetric outcome of the manual adaptive planning during definitive radiotherapy for cervical cancer.

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.

Estimating pathological prognostic factors in epithelial ovarian cancers using apparent diffusion coefficients of functional tumor volume.

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.

Cross-ancestry genome-wide association studies of brain imaging phenotypes.

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.

SAH is a major metabolic sensor mediating worsening metabolic crosstalk in metabolic syndrome.

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.

Prevalence and related factors of sleep quality among Chinese undergraduates in Jiangsu Province: multiple models' analysis.

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.

Nitric oxide mediates red light-induced perylenequinone production in Shiraia mycelium culture.

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.

Diagnostic value of LGE and T1 mapping in multiple myeloma patients'heart.

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.

Copper(I)-Catalyzed Indolyl Ynamide Oxidation/Dearomatization: Divergent and Regioselective Synthesis of Valuable Indoline Scaffolds.

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.