Widely targeted metabolomics-based analysis of the impact of L. plantarum and L. paracasei fermentation on rosa roxburghii Tratt juice.

Rosa roxburghii Tratt fruits (RRT) exhibit extremely high nutritional and medicinal properties due to its unique phytochemical composition. Probiotic fermentation is a common method of processing fruits. Variations in the non-volatile metabolites and bioactivities of RRT juice caused by different lactobacilli are not well understood. Therefore, we aimed to profile the non-volatile components and investigate the impact of L. plantarum fermentation (LP) and L. paracasei fermentation (LC) on RRT juice (the control, CG). There were both similarities and differences in the effects of LP and LC on RRT juice. Both of the two strains significantly increased the content of total phenolic, total flavonoid, and some bioactive compounds such as 2-hydroxyisocaproic acid, hydroxytyrosol and indole-3-lactic acid in RRT juice. Interestingly, compared with L. paracasei, L. plantarum showed better ability to increase the content of total phenolic and these valuable compounds, as well as certain bioactivities. The antioxidant capacity and α-glucosidase inhibitory activity of RRT juice were notably enhanced after the fermentations, whereas its cholesterol esterase inhibitory activity was reduced significantly. Moreover, a total of 1466 metabolites were identified in the unfermented and fermented RRT juices. There were 278, 251 and 134 differential metabolites in LP vs CG, LC vs CG, LC vs LP, respectively, most of which were upregulated. The key differential metabolites were classified into amino acids and their derivatives, organic acids, nucleotides and their analogues, phenolic acids and alkaloids, which can serve as potential markers for authentication and discrimination between the unfermented and lactobacilli fermented RRT juice samples. The KEGG enrichment analysis uncovered that metabolic pathways, purine metabolism, nucleotide metabolism and ABC transporters contributed mainly to the formation of unique composition of fermented RRT juice. These results provide good coverage of the metabolome of RRT juice in both unfermented and fermented forms and also provide a reference for future research on the processing of RRT or other fruits.

Characterization and prebiotic potential of polysaccharides from Rosa roxburghii Tratt pomace by ultrasound-assisted extraction.

In this study, polysaccharides (RRTPs) were extracted from Rosa roxburghii Tratt pomace by hot water or ultrasound (US)-assisted extraction. The structural properties and potential prebiotic functions of RRTPs were investigated. Structural characterization was conducted through HPAEC, HPGPC, GC-MS, FT-IR and SEM. Chemical composition analysis revealed that RRTPs extracted by hot water (RRTP-HW) or US with shorter (RRTP-US-S) or longer duration (RRTP-US-L) all consisted of galacturonic acid, galactose, glucose, arabinose, rhamnose and glucuronic acid in various molar ratio. US extraction caused notable reduction in molecular weight of RRTPs but no significant changes in primary structures. Fecal fermentation showed RRTPs could reshape microbial composition toward a healthier balance, leading to a higher production of beneficial metabolites including total short-chain fatty acids, curcumin, noopept, spermidine, 3-feruloylquinic acid and citrulline. More beneficial shifts in bacterial population were observed in RRTP-HW group, while RRTP-US-S had stronger ability to stimulate bacterial short-chain fatty acids production. Additionally, metabolic profiles with the intervention of RRTP-HW, RRTP-US-S or RRTP-US-L were significantly different from each other. The results suggested RRTPs had potential prebiotic effects which could be modified by power US via molecular weight degradation.

Characterization of bacterial diversity and screening of cellulose-degrading bacteria in the gut system of Glenea cantor (Fabricius) larvae.

The intestinal bacteria of longhorn beetles would be ideal targets for pest control and lignocellulosic resources by destroying or exploiting their cellulose-degrading function. This article aims to investigate the diversity and community structure of intestinal bacteria the oligophagous longhorn beetle Glenea cantor. Additionally, it seeks to identify the presence of lignocellulose-degrading bacteria in the gut, and explore their role in consuming host kapok trees Bombax malabaricum. In this study, the bacterial community from G. cantor was examined by Illumina sequencing of 16S ribosomal RNA (rRNA) targeting the V3 and V4 regions. A total of 563,201 valid sequences and 814 OTUs were obtained. The dominant phyla were Proteobacteria, and the dominant genera were Acinetobacter and Lactococcus. The analysis of microbial diversity revealed a high bacterial diversity in the samples, with the gut bacteria playing a crucial role in the physiological activities of the host, particularly, 9 genera of intestinal bacteria with cellulose degradation function were found, highlighting their vital role in cellulose degradation. Five strains of cellulose-degrading bacteria, belonging to the genus Pseudomonas, were obtained from the intestinal tract of G. cantor larvae using traditional isolation and culture techniques as well as 16S rDNA sequencing. Among these strains, A4 exhibited a cellulase activity of 94.42 ± 0.42 U/mL, while A5 displayed the highest filter paper enzyme activity of 127.46 ± 3.54 U/mL. These results offered valuable insights into potential targets for pest control through internal attack digestion and cellulose-degrading bacteria in longhorn beetles.

Physical Stimulation Methods Developed for In Vitro Neuronal Differentiation Studies of PC12 Cells: A Comprehensive Review.

PC12 cells, which are derived from rat adrenal pheochromocytoma cells, are widely used for the study of neuronal differentiation. NGF induces neuronal differentiation in PC12 cells by activating intracellular pathways via the TrkA receptor, which results in elongated neurites and neuron-like characteristics. Moreover, the differentiation requires both the ERK1/2 and p38 MAPK pathways. In addition to NGF, BMPs can also induce neuronal differentiation in PC12 cells. BMPs are part of the TGF-ß cytokine superfamily and activate signaling pathways such as p38 MAPK and Smad. However, the brief lifespan of NGF and BMPs may limit their effectiveness in living organisms. Although PC12 cells are used to study the effects of various physical stimuli on neuronal differentiation, the development of new methods and an understanding of the molecular mechanisms are ongoing. In this comprehensive review, we discuss the induction of neuronal differentiation in PC12 cells without relying on NGF, which is already established for electrical, electromagnetic, and thermal stimulation but poses a challenge for mechanical, ultrasound, and light stimulation. Furthermore, the mechanisms underlying neuronal differentiation induced by physical stimuli remain largely unknown. Elucidating these mechanisms holds promise for developing new methods for neural regeneration and advancing neuroregenerative medical technologies using neural stem cells.

[Clinical characteristics and prognosis of children with perianal fistulizing Crohn's disease]. / å„¿ç«¥è‚›å‘¨ç˜˜ç®¡åž‹å ‹ç½—æ©ç— çš„ä¸´åºŠç‰¹å¾åŠé¢„åŽ.

OBJECTIVES: To investigate the clinical characteristics, treatment, and prognosis of children with perianal fistulizing Crohn's disease (pfCD). METHODS: A retrospective analysis was conducted on the children, aged 6-17 years, who were diagnosed with Crohn's disease (CD) from April 2015 to April 2023. According to the presence or absence of perianal fistulizing lesions, they were divided into two groups: pfCD (n=60) and non-pfCD (n=82). The two groups were compared in terms of clinical characteristics, treatment, and prognosis. RESULTS: The incidence of pfCD was 42.3% (60/142). The proportion of males in the pfCD group was higher than that in the non-pfCD group. Compared with the non-pfCD group, the pfCD group had a significantly higher proportion of children with involvement of the colon and small intestine or those with upper gastrointestinal lesions (P<0.05). Compared with the non-pfCD group, the pfCD group had a significantly higher rate of use of infliximab during both induction and maintenance treatment (P<0.05). In the pfCD group, the children with complex anal fistula accounted for 62% (37/60), among whom the children receiving non-cutting suspended line drainage accounted for 62% (23/37), which was significantly higher than the proportion among the children with simple anal fistula patients (4%, 1/23) (P<0.05). There were no significant differences between the two groups in mucosal healing rate and clinical remission rate at week 54 of treatment (P>0.05). The pfCD group achieved a fistula healing rate of 57% (34/60) at week 54, and the children with simple anal fistula had a significantly higher rate than those with complex anal fistula (P<0.05). CONCLUSIONS: There is a high incidence rate of pfCD in children with CD, and among the children with pfCD, there is a high proportion of children with the use of biological agents. There is a high proportion of children receiving non-cutting suspended line drainage among the children with complex anal fistula. The occurrence of pfCD should be closely monitored during the follow-up in children with CD.

Anti-apoptotic effect of adrenomedullin gene delivery on Leydig cells by suppressing TGF-ß1 via the Hippo signaling pathway.

This study aims to establish whether adrenomedullin (ADM) is capable to restore the steroidogenic functions of Leydig cells by suppressing transforming growth factor-ß1 (TGF-ß1) through Hippo signaling. Primary Leydig cells were treated with lipopolysaccharide (LPS), an adeno-associated virus vector that expressed ADM (Ad-ADM) or sh-RNA of TGF-ß1 (Ad-sh-TGF-ß1). The cell viability and medium concentrations of testosterone were detected. Gene expression and protein levels were determined for steroidogenic enzymes, TGF-ß1, RhoA, YAP, TAZ and TEAD1. The role of Ad-ADM in the regulation of TGF-ß1 promoter was confirmed by ChIP and Co-IP. Similar to Ad-sh-TGF-ß1, Ad-ADM mitigated the decline in the number of Leydig cells and plasma concentrations of testosterone by restoring the gene and protein levels of SF-1, LRH1, NUR77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD. Similar to Ad-sh-TGF-ß1, Ad-ADM not only inhibited the LPS-induced cytotoxicity and cell apoptosis but also restored the gene and protein levels of SF-1, LRH1, NUR77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD, along with the medium concentrations of testosterone in LPS-induced Leydig cells. Like Ad-sh-TGF-ß1, Ad-ADM improved LPS-induced TGF-ß1 expression. In addition, Ad-ADM suppressed RhoA activation, enhanced the phosphorylation of YAP and TAZ, reduced the expression of TEAD1 which interacted with HDAC5 and then bound to TGF-ß1 gene promoter in LPS-exposed Leydig cells. It is thus suspected that ADM can exert anti-apoptotic effect to restore the steroidogenic functions of Leydig cells by suppressing TGF-ß1 through Hippo signaling.

Cu-MOFs based photocatalyst triggered antibacterial platform for wound healing: 2D/2D Schottky junction and DFT calculation.

Herein, we developed a multimodal antibacterial nanoplatform via synergism effect including knife-effect, photothermal, photocatalytic induced reactive oxygen species (ROS), and Cu2+ inherent attribute. Typically, 0.8-TC/Cu-NS possesses higher photothermal property with the higher photothermal conversion efficiency of 24% and the moderate temperature up to 97 °C. Meanwhile, 0.8-TC/Cu-NS exhibits the more active ROS, 1O2 and ·O2-. Hence, 0.8-TC/Cu-NS possesses best antibacterial properties against S. aureus and E. coli in vitro with efficiency of 99.94%/99.97% under near-infrared (NIR) light, respectively. In the therapeutic practical use for wound healing of Kunming mice, this system exhibits outstanding curing capacity and good biocompatibility. Based on the electron configuration measurement and density functional theory (DFT) simulation, it is confirmed that the electrons on CB of Cu-TCPP flow fleetingly to MXene trough the interface, with redistribution of charge and band upward bending over Cu-TCPP. As a result, the self-assembled 2D/2D interfacial Schottky junction have made great favor to accelerate photogenerated charges mobility, hamper charge recombination, and increases the photothermal/photocatalytic activity. This work gives us a hint to mostly design the multimodal synergistic nanoplatform under NIR light in biological applications without drug resistance.

Four New Polyhydroxy Cyclohexanes from the Stems of Fissistigma tientangense.

Four undescribed polyhydroxy cyclohexanes, fissoxhydrylenes A-D (1-4), together with two known biogenetically related polyhydroxy cyclohexanes (5 and 6) were isolated from the stems of Fissistigma tientangense Tsiang et P. T. Li. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR, UV and Optical rotations data. The absolute configuration of 1 was confirmed by X-ray crystallographic. The absolute configurations of 2-4 were confirmed by chemical reaction and optical rotations. Compound 4 represent the first example of a no substituent polyhydroxy cyclohexanes from natural products. All isolated compounds were evaluated for their anti-inflammatory activities against the lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells in vitro. Compounds 3 and 4 showed inhibitory activities with the IC50 values of 16.63±0.06 µM and 14.38±0.08 µM, respectively.

Guaiane-Type Sesquiterpenes from the Stems of Fissistigma oldhamii.

Two new guaiane-type sesquiterpenes dysodensiols J and L, one new natural product dysodensiol K together with four known biogenetically related guaiane-type sesquiterpenes were isolated from the stems of Fissistigma oldhamii. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR and Optical rotations data. Compound 1 contains an uncommon five-membered ether ring. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed inhibitory activity with an IC50 value of 6.8 µM. Compounds 5-7 exhibited moderate inhibitory activity with IC50 values of 23.8, 26.6, and 27.1 µM, respectively.

Consensus for criteria of running a pediatric inflammatory bowel disease center using a modified Delphi approach.

BACKGROUND: Good quality of care for inflammatory bowel disease (IBD) depends on high-standard management and facility in the IBD center. Yet, there are no clear measures or criteria for evaluating pediatric IBD (PIBD) center in China. The aim of this study was to develop a comprehensive set of quality indicators (QIs) for evaluating PIBD center in China. METHODS: A modified Delphi consensus-based approach was used to identify a set of QIs of structure, process, and outcomes for defining the criteria. The process included an exhaustive search using complementary approaches to identify potential QIs, and two web-based voting rounds to select the QIs defining the criteria for PIBD center. RESULTS: A total of 101 QIs (35 structures, 48 processes and 18 outcomes) were included in this consensus. Structure QIs focused on the composition of multidisciplinary team, facilities and services that PIBD center should provide. Process QIs highlight core requirements in diagnosing, evaluating, treating PIBD, and disease follow-up. Outcome QIs mainly included criteria evaluating effectiveness of various interventions in PIBD centers. CONCLUSION: The present Delphi consensus developed a set of main QIs that may be useful for managing a PIBD center. Video Abstract.

Evaluation of heavy metal pollution with uneven spatial sampling distribution based on Voronoi area density.

Ecological risk index and Voronoi diagram have been extensively used as a diagnostic guide for heavy metal pollution to support people in-depth analysis of the possibility of various contamination sources causing damage to social production, life, and the ecological environment. However, under the condition of uneven distribution of detection points, there are often situations where the Voronoi polygon area corresponding to a large degree of pollution is small or the area of the Voronoi polygon is great with a low level of pollution, and using the Voronoi area weighting or the Voronoi area density may ignore heavily polluted local areas. This study proposes the Voronoi density-weighted summation to accurately measure the concentration and diffusion of heavy metal pollution in the target area for the above issues. Then, we propose a contribution value method based on k-means to determine the number of divisions to ensure the prediction accuracy and computational cost at the same time. Moreover, applying local entropy deepens the understanding of local regional and overall system situations. Through four representative regions, the results show that the proposed whole scheme based on Voronoi diagram can effectively predict and evaluate the spatial distribution of heavy metal pollution, which provides a theoretical basis for comprehending and exploring the complex pollution environment.

BuresNet: Conditional Bures Metric for Transferable Representation Learning.

As a fundamental manner for learning and cognition, transfer learning has attracted widespread attention in recent years. Typical transfer learning tasks include unsupervised domain adaptation (UDA) and few-shot learning (FSL), which both attempt to sufficiently transfer discriminative knowledge from the training environment to the test environment to improve the model's generalization performance. Previous transfer learning methods usually ignore the potential conditional distribution shift between environments. This leads to the discriminability degradation in the test environments. Therefore, how to construct a learnable and interpretable metric to measure and then reduce the gap between conditional distributions is very important in the literature. In this article, we design the Conditional Kernel Bures (CKB) metric for characterizing conditional distribution discrepancy, and derive an empirical estimation with convergence guarantee. CKB provides a statistical and interpretable approach, under the optimal transportation framework, to understand the knowledge transfer mechanism. It is essentially an extension of optimal transportation from the marginal distributions to the conditional distributions. CKB can be used as a plug-and-play module and placed onto the loss layer in deep networks, thus, it plays the bottleneck role in representation learning. From this perspective, the new method with network architecture is abbreviated as BuresNet, and it can be used extract conditional invariant features for both UDA and FSL tasks. BuresNet can be trained in an end-to-end manner. Extensive experiment results on several benchmark datasets validate the effectiveness of BuresNet.

Case report: Application of nonsurgical method in saving transplant renal vein thrombosis caused by acute diarrhea.

Transplant renal vein thrombosis is a rare complication after kidney transplantation, which can seriously threaten graft survival. Though the measures like thrombolytic therapy or operative intervention could be taken to deal with this complication, allograft loss is the most common outcome. Thus, early finding as well as decisive intervention is crucial to saving the graft. Here we present a 46-year-old male patient who underwent kidney transplantation from a cadaveric donor who developed a transplant renal venous thrombosis induced by acute diarrhea more than 1 year after renal transplantation with an initial symptom of sudden anuria and pain in the graft area. Subsequently, serum creatinine levels increased to 810.0 µmol/L. Pelvic CT showed increased vascular density of the transplanted kidney, and contrast-enhanced ultrasound confirmed venous thrombosis. The patient was treated with heparin sodium alone and diuresis gradually resumed. After more than 1 year of follow-up, serum creatinine returned to the baseline level prior to thrombosis. Our case indicates that quick ancillary examination and treatment without hesitation would be indispensable in rescuing allografts with renal vein thrombus. Unfractionated heparin can be recommended as an effective treatment for mid-long-term renal transplantation patients with renal vein thrombosis.

SP600125 Enhances Temperature-Controlled Repeated Thermal Stimulation-Induced Neurite Outgrowth in PC12-P1F1 Cells.

This study evaluated the mechanism of temperature-controlled repeated thermal stimulation (TRTS)-mediated neuronal differentiation. We assessed the effect of SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, on neuronal differentiation of rat PC12-P1F1 cells, which can differentiate into neuron-like cells by exposure to TRTS or neurotrophic factors, including bone morphogenetic protein (BMP) 4. We evaluated neuritogenesis by incubating the cells under conditions of TRTS and/or SP600125. Cotreatment with SP600125 significantly enhanced TRTS-mediated neuritogenesis, whereas that with other selective mitogen-activated protein kinase (MAPK) inhibitors did not-e.g., extracellular signal-regulated kinase (ERK)1/2 inhibitor U0126, and p38 MAPK inhibitor SB203580. We tried to clarify the mechanism of SP600125 action by testing the effect of U0126 and the BMP receptor inhibitor LDN193189 on the SP600125-mediated enhancement of intracellular signaling. SP600125-enhanced TRTS-induced neuritogenesis was significantly inhibited by U0126 or LDN193189. Gene expression analysis revealed that TRTS significantly increased ß3-Tubulin, MKK3, and Smad7 gene expressions. Additionally, Smad6 and Smad7 gene expressions were substantially attenuated through SP600125 co-treatment during TRTS. Therefore, SP600125 may partly enhance TRTS-induced neuritogenesis by attenuating the negative feedback loop of BMP signaling. Further investigation of the mechanisms underlying the effect of SP600125 during TRTS-mediated neuritogenesis may contribute to the future development of regenerative neuromedicine.

Local adrenomedullin gene delivery inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo.

Adrenomedullin (ADM) has beneficial effects on Leydig cells under pathological conditions, including lipopolysaccharide (LPS)-induced orchitis. Our previous studies demonstrated that ADM exerts a restorative effect on steroidogenesis in LPS-treated primary rat Leydig cells by attenuating oxidative stress, inflammation and apoptosis. In this study, we aim to investigate whether ADM inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo. Rats were administered with LPS and injected with Ad-ADM, an adeno-associated virus vector that expressed ADM. Then, rat testes were collected for 3ß-hydroxysteroid dehydrogenase (3ß-HSD) immunofluorescence staining. Steroidogenic enzymes or steroidogenic regulatory factors or protein, including steroidogenic factor-1 (SF-1), liver receptor homologue-1 (LRH1), Nur77, steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc), 3ß-HSD, cytochrome P450 17α-hydroxylase/17, 20 lyase (CYP17) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD), were detected via gene expression profiling and western blot analysis. Plasma testosterone concentrations were measured. Results showed that ADM may inhibit Leydig cell dysfunction by rescuing steroidogenic enzymes and steroidogenic regulatory factors in vivo. The reduction in the number of Leydig cells after LPS exposure was reversed by ADM. ADM rescued the gene or protein levels of SF-1, LRH1, Nur77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD and plasma testosterone concentrations. To summarize ADM could rescue some important steroidogenic enzymes, steroidogenic regulatory factors and testosterone production in Leydig cells in vivo.

Inhibition of PLK3 Attenuates Tubular Epithelial Cell Apoptosis after Renal Ischemia-Reperfusion Injury by Blocking the ATM/P53-Mediated DNA Damage Response.

Objective: Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI) in transplanted kidneys. This study was aimed at exploring the role of PLK3 (polo-like kinase 3) in renal I/R injury, focusing on its relationship with oxidative stress-induced DNA damage and renal tubular epithelial cell (TEC) apoptosis. Methods: TRAP-seq data from the development dataset GSE52004 and the validation dataset GSE121191 were analyzed using GEO2R. PLK3 overexpression plasmids and targeted silencing siRNAs were used in a model of hypoxia/reoxygenation (H/R) injury, and rAAV-9-PLK3-KD were administered to C57BL/6J mice exposed to I/R injury. The ATM-specific inhibitor KU-60019 was used to block the DNA damage response (DDR). Western blotting was performed to measure DDR- and apoptosis-associated protein expression. Cell viability was measured by CCK-8 reagent, and apoptosis was examined by flow cytometry and TUNEL assay. Furthermore, the fluorescent probes H2DCFH-DA and DHE were used to measure ROS production in vitro. The MDA level and SOD activity were measured to assess oxidative stress in vivo. KIM-1 staining and Scr and BUN were used to evaluate kidney injury. Results: The mRNA and protein levels of PLK3 were markedly increased in the H/R injury and I/R injury models. GO terms showed that PLK3 was mainly involved in oxidative stress and DNA damage after renal I/R injury. Overexpression of PLK3 decreased cell viability and increased apoptosis. In contrast, targeted silencing of PLK3 expression decreased the Bax/Bcl-2 ratio by decreasing P53 phosphorylation, thereby reducing TEC apoptosis. Furthermore, KU-60019 reduced PLK3 activation and DDR-induced apoptosis, while overexpression of PLK3 reversed the mitigating effect of KU-60019 on TEC apoptosis. Similarly, rAAV-9-PLK3 KD mice exhibited a lower rate of TEC apoptosis and milder renal damage after I/R injury. Conclusion: We demonstrate for the first time that PLK3 is involved in oxidative stress-induced DNA damage and TEC apoptosis in renal I/R injury. Inhibition of PLK3 attenuates TEC apoptosis after I/R injury by blocking the ATM/P53-mediated DDR. Therefore, PLK3 may serve as a potential therapeutic target for ischemic AKI.

Talaromarins A-F: Six New Isocoumarins from Mangrove-Derived Fungus Talaromyces flavus TGGP35.

Six new isocoumarin derivative talaromarins A-F (1-6), along with 17 known analogues (7-23), were isolated from the mangrove-derived fungus Talaromyces flavus (Eurotiales: Trichocomaceae) TGGP35. Their structures were identified by detailed IR, UV, 1D/2D NMR and HR-ESI-MS spectra. The absolute configurations of new compounds were determined by the modified Mosher's method and a comparison of their CD spectra with dihydroisocoumarins described in the literature. The antioxidant, antibacterial, anti-phytopathogenic and inhibitory activity against α-glucosidase of all the isolated compounds were tested. Compounds 6-11, 17-19 and 21-22 showed similar or better antioxidant activity than the IC50 values ranging from 0.009 to 0.27 mM, compared with the positive control trolox (IC50 = 0.29 mM). Compounds 10, 18, 21 and 23 exhibited strong inhibitory activities against α-glucosidase with IC50 values ranging from 0.10 to 0.62 mM, while the positive control acarbose had an IC50 value of 0.5 mM. All compounds showed no antibacterial or anti-phytopathogenic activity at the concentrations of 50 µg/mL and 1 mg/mL, respectively. These results indicated that isocoumarins will be useful to developing antioxidants and as diabetes control agents.

[Effectiveness of induction therapy with exclusive enteral nutrition in pediatric Crohn's disease]. / å ¨è‚ å† è¥å »å¯¹å„¿ç«¥å ‹ç½—æ©ç— è¯±å¯¼ç¼“è§£ç–—æ•ˆç ”ç©¶.

OBJECTIVES: To evaluate the effectiveness of induction therapy with exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD). METHODS: A retrospective analysis was performed on the medical data of 62 children with CD who received EEN in Children's Hospital, Zhejiang University School of Medicine, from March 2013 to August 2021. The medical data included general information and height, weight, Pediatric Crohn's Disease Activity Index (PCDAI), Crohn's Disease Endoscopic Index of Severity, C-reactive protein, erythrocyte sedimentation rate, and serum albumin level before treatment and after 8 weeks of treatment. The changes in the above indicators were compared before and after treatment. RESULTS: Among the 62 children with CD, there were 39 boys (63%) and 23 girls (37%), with a mean age of (11.9±3.0) years at diagnosis. Among the 55 children who completed EEN treatment for at least 8 weeks, 48 (87%) achieved clinical remission at week 8. PCDAI at week 8 was significantly lower than that before treatment (P<0.001). Except for 17 children with involvement of the small intestine alone and 3 children with involvement of the colon who did not receive colonoscopy reexamination, the remaining 35 children with involvement of the colon received colonoscopy reexamination after the 8-week EEN treatment. Of the 35 children, 29 (83%) achieved mucosal healing. As for the 48 children who achieved clinical remission at week 8, there were significant improvements in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P<0.01). As for the 7 children who did not achieve clinical remission at week 8, there were no significant changes in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P>0.05). CONCLUSIONS: The 8-week EEN treatment has a good effect on clinical remission and mucosal healing in children with CD. For the children with CD achieving clinical remission, EEN can improve their height and body mass index.

Redox Metabolism-Associated Molecular Classification of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. Redox metabolism has been recognized as the hallmark of cancer. But the concrete role of redox-related genes in patient stratification of ccRCC remains unknown. Herein, we aimed to characterize the molecular features of ccRCC based on the redox gene expression profiles from The Cancer Genome Atlas. Differentially expressed redox genes (DERGs) and vital genes in metabolism regulation were identified and analyzed in the ccRCC. Consensus clustering was performed to divide patients into three clusters (C1, C2, and C3) based on 139 redox genes with median FPKM value > 1. We analyzed the correlation of clusters with clinicopathological characteristics, immune infiltration, gene mutation, and response to immunotherapy. Subclass C1 was metabolic active with moderate prognosis and associated with glucose, lipid, and protein metabolism. C2 had intermediate metabolic activity with worse prognosis and correlated with more tumor mutation burden, neoantigen, and aneuploidy, indicating possible drug sensitivities towards immune checkpoint inhibitors. Metabolic exhausted subtype C3 showed high cytolytic activity score, suggesting better prognosis than C1 and C2. Moreover, the qRT-PCR was performed to verify the expression of downregulated DERGs including ALDH6A1, ALDH1L1, GLRX5, ALDH1A3, and GSTM3, and upregulated SHMT1 in ccRCC. Overall, our study provides an insight into the characteristics of molecular classification of ccRCC patients based on redox genes, thereby deepening the understanding of heterogeneity of ccRCC and allowing prediction of prognosis of ccRCC patients.

Rare isotachin-derived from the Dasymaschalon rostratum fungus Penicillium tanzanicum ZY-5.

Four rare isotachin-derived, isotachins E-H (1-4), together with two known biogenetically related isotachin derivatives (5 and 6) were isolated from the solid rice fermentation of a fungus Penicillium tanzanicum ZY-5 obtained from a medicinal plant Dasymaschalon rostratum collected from the Changjiang County, Hainan Province, China. Their structures were elucidated using comprehensive spectroscopic methods. The single-crystal X-ray diffraction of compound 5 was determined. Compounds 1-4 have a trans-3-(methylthio)-acrylic acid fragment, which are rare in nature. The inhibitory activities of all compounds against the nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro were evaluated.