Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange.

Modular SCF (SKP1-CUL1-Fbox) ubiquitin E3 ligases orchestrate multiple cellular pathways in eukaryotes. Their variable SKP1-Fbox substrate receptor (SR) modules enable regulated substrate recruitment and subsequent proteasomal degradation. CAND proteins are essential for the efficient and timely exchange of SRs. To gain structural understanding of the underlying molecular mechanism, we reconstituted a human CAND1-driven exchange reaction of substrate-bound SCF alongside its co-E3 ligase DCNL1 and visualized it by cryo-EM. We describe high-resolution structural intermediates, including a ternary CAND1-SCF complex, as well as conformational and compositional intermediates representing SR- or CAND1-dissociation. We describe in molecular detail how CAND1-induced conformational changes in CUL1/RBX1 provide an optimized DCNL1-binding site and reveal an unexpected dual role for DCNL1 in CAND1-SCF dynamics. Moreover, a partially dissociated CAND1-SCF conformation accommodates cullin neddylation, leading to CAND1 displacement. Our structural findings, together with functional biochemical assays, help formulate a detailed model for CAND-SCF regulation.

ß-Ga2O3nanotube arrays for high-performance self-powered ultraviolet photoelectrochemical photodetectors.

Self-powered ultraviolet (UV) photodetectors (PDs) are critical for future energy-efficient optoelectronic systems due to their low energy consumption and high sensitivity. In this paper, the vertically alignedß-Ga2O3nanotube arrays (NTs) have been prepared on GaN/sapphire substrate by the thermal oxidation process combined with the dry etching technology, and applied in the UV photoelectrochemical photodetectors (PEC-PDs) for the first time. Based on the large specific surface area ofß-Ga2O3NTs on GaN/sapphire substrates and the solid/liquid heterojunction, the PEC-PDs exhibit excellent self-powered characteristics under 255 nm (UVA) and 365 nm (UVC) light illumination. Under 255 nm (365 nm) light illumination, the maximum responsivity of 49.9 mA W-1(32.04 mA W-1) and a high detectivity of 1.58 × 1011Jones (1.01 × 1011Jones) were achieved for theß-Ga2O3NTs photodetectors at 0 V bias. In addition, the device shows a fast rise/decay time of 8/4 ms (4/2 ms), which is superior to the level of the previously reported self-powered UV PEC-PDs. This high-performance PEC-PD has potential applications in next-generation low-energy UV detection systems.

[Effect of Erchen Decoction on liver mitochondrial function by inhibiting mTORC1/SREBP1/CAV1 pathway in mice with high-fat diet].

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.

Modulating of Bouligand Structure and Chirality Constructed Bionically Based on the Self-Assembly of Chitin Whiskers.

Chitin can self-assemble into a liquid crystal phase with supramolecular chirality and Bouligand structure, which is widely found in the exoskeletons of arthropods. However, bionically replicating this structure via the self-assembly of chitin whiskers (CHWs) is still a challenge. Here, the effects of several internal and external parameters on the self-assembly of CHWs were revealed based on liquid crystal phase, chirality, Bouligand structure, and rheological properties. The formation of chiral liquid crystal phase and Bouligand structure largely depends on the concentration of CHWs and, meanwhile, is affected by the aspect ratio and zeta potential of CHWs and the self-assembly time. Impressively, introducing electrolytes and changing pH significantly affect the thickness of the electrical double layer, thereby also affecting the self-assembly of CHWs. This study offers a comprehensive understanding of CHWs' self-assembly process, which is beneficial for the bionic design of new nature-inspired functional materials with chiral characteristic and Bouligand structure.

Association between the insulin resistance marker TyG index and subsequent adverse long-term cardiovascular events in young and middle-aged US adults based on obesity status.

BACKGROUND: A lthough the triglyceride-glucose (TyG) index has been shown to closely correlate with cardiometabolic outcomes and predict cardiovascular events in many groups, it remains unclear whether obese status in young and middle-aged adults is associated with long-term unfavorable cardiovascular events. This warrants further investigation. METHODS: This retrospective cohort study analyzed data from the National Health and Nutrition Examination Survey spanning the years 1999-2018, with follow-up for mortality status until December 31, 2019. To categorize participants based on the TyG level, the optimal critical value was determined through restricted cubic spline function analysis, dividing them into high and low TyG groups. The study assessed the relationship between TyG and cardiovascular events and all-cause mortality in young and middle-aged adults stratified by obesity status. Kaplan‒Meier and Cox proportional risk models were used to analyze the data. RESULTS: During a follow-up period of 123 months, a high TyG index increased the risk of cardiovascular events by 63% (P = 0.040) and the risk of all-cause mortality by 32% (P = 0.010) in individuals after adjusting for all covariates. High TyG was shown to be linked to cardiovascular events in obese people (Model 3: HR = 2.42, 95% CI = 1.13-5.12, P = 0.020); however, there was no significant difference in TyG groups for nonobese adults in Model 3 (P = 0.08). CONCLUSIONS: TyG was independently associated with harmful long-term cardiovascular events in young and middle-aged US populations, with a stronger association observed in those who were obese.

Assessment of the impact of shift work on thyroid disorders: a systematic review and meta-analysis.

PURPOSE: Shift work including night work is a common work pattern worldwide and researchers have no consensus on the impact of shift work on thyroid disorders. We aimed to conduct a meta-analysis to summarize the evidence from published studies to ascertain the impact of shift work on thyroid disorders. METHODS: Studies on the link between shift work and thyroid disorders published in Pubmed, Embase, Medline, and Cochrane databases by September 2021 were searched. Newcastle-Ottawa scale was used to assess the quality of included studies. The Mantel-Haenszel statistical method and the inverse-variance statistical method were used to evaluate the pooled results of dichotomous and continuous variables, respectively. Study heterogeneity analysis was performed using I2 statistics. Sensitivity analysis was conducted by omitting one study each time and re-calculating the pooled results of the remaining studies. RESULTS: Seven eligible studies were included in the systematic review and meta-analysis. The results showed that shift work would lead to an increase in TSH (SMD: 0.30; 95%CI: 0.05-0.55; P = 0.02; I2 = 64%) and FT4 (SMD: 0.21; 95%CI: 0.02-0.40; P = 0.03; I2 = 0%). However, shift work had no clear effect on the risk of positive thyroid autoantibodies (OR: 1.26; 95%CI: 0.62-2.55; P = 0.52; I2 = 63%). CONCLUSION: Shift work may be associated with abnormal TSH and FT4 levels. Thyroid health is affected in shift workers and it is advisable to remind patients to get good sleep the night before testing thyroid function.

Xanthones from Gentianella acuta (Michx.) Hulten Ameliorate Colorectal Carcinoma via the PI3K/Akt/mTOR Signaling Pathway.

Colorectal carcinoma (CRC) is a kind of malignant tumor closely related to ulcerative colitis. Xanthone derivatives are one of the most promising therapeutic drugs which have been used in phase I/II clinical trials for cancer therapy. Our previous study indicated that the aerial parts of Gentianella acuta Michx. Hulten (GA) was rich in xanthones and showed a good therapeutic effect on ulcerative colitis in mice, suggesting that GA xanthones might have some therapeutic or ameliorative effects on CRC. However, no relevant study has been reported. This study aims to find the effective substances of GA inhibiting CRC and clarify their mechanism. Solvent extraction, column chromatographic separation, and LC-MS analysis were used to characterize the 70% EtOH extract of GA and track xanthones abundant fraction XF. MTT assay was carried out to clarify the activity of GA fractions; the result showed XF to be the main active fraction. LC-MS analysis was executed to characterize XF, 38 xanthones were identified. Network pharmacology prediction, in vitro activity screening, and molecular docking assay were combined to predict the potential mechanism; the PI3K/Akt/mTOR signaling pathway was found to be most important. Western blot assay on the main active xanthones 1,3,5-trihydroxyxanthone (16), 1,3,5,8-tetrahydroxyxanthone (17), 1,5,8-trihydroxy-3-methoxyxanthone (18), and 1,7-dihydroxy-3,8-dimethoxyxanthone (19) was used to verify the above prediction; these xanthones were found to inhibit the PI3K/Akt/mTOR signaling pathway, and 17 played a significant role among them through Western blot assay using PI3K/AKT/mTOR agonist IGF-1. In conclusion, this study demonstrated that GA xanthones were effective compounds of GA inhibiting CRC by regulating PI3K/Akt/mTOR signaling pathway transduction, at least. Importantly, 1,3,5,8-tetrahydroxyxanthone (17), the most abundant active xanthone in GA, might be a candidate drug for CRC.

Polyphenols from the Peels of Punica granatum L. and Their Bioactivity of Suppressing Lipopolysaccharide-Stimulated Inflammatory Cytokines and Mediators in RAW 264.7 Cells via Activating p38 MAPK and NF-κB Signaling Pathways.

Punica granatum L. (Punicaceae) is a popular fruit all over the world. Owning to its enriched polyphenols, P. granatum has been widely used in treating inflammation-related diseases, such as cardiovascular diseases and cancer. Twenty polyphenols, containing nine unreported ones, named punicagranins A-I (1-9), along with eleven known isolates (10-20), were obtained from the peels. Their detailed structures were elucidated based on UV, IR, NMR, MS, optical rotation, ECD analyses and chemical evidence. The potential anti-inflammatory activities of all polyphenols were examined on a lipopolysaccharide (LPS)-induced inflammatory macrophages model, which indicated that enhancing nitric oxide (NO) production in response to inflammation stimulated in RAW 264.7 cells was controlled by compounds 1, 3, 5-8, 10, 11, 14 and 16-20 in a concentration-dependent manner. The investigation of structure-activity relationships for tannins 6-8 and 12-20 suggested that HHDP, flavogallonyl and/or gallagyl were key groups for NO production inhibitory activity. Western blotting indicated that compounds 6-8 could down-regulate the phosphorylation levels of proteins p38 MAPK, IKKα/ß, IκBα and NF-κB p65 as well as inhibit the levels of inflammation-related cytokines and mediators, such as IL-6, TNF-α, iNOS and COX-2, at the concentration of 30 µM. In conclusion, polyphenols are proposed to be the potential anti-inflammatory active ingredients in P. granatum peels, and their molecular mechanism is likely related to the regulation of the p38 MAPK and NF-κB signaling pathways.

Biomimetic FeMo(Se, Te) as Joint Electron Pool Promoting Nitrogen Electrofixation.

It has been long believed that the FeMoS structure, where Fe is bonded with S, plays a pivotal role as a biomimetic catalyst for electrochemical nitrogen (N2 ) fixation. Nevertheless, the structure of Fe bonded to heavier analogues (Se or Te) has never been explored for N2 electrofixation. Here, we theoretically predict the electronic structure of FeMo(Se, Te) composed of tri-coordinated Fe species with open shells for binding with Se, which forms a joint electron pool for promoting N2 activation. Guided by this interesting prediction, we then demonstrate a two-step procedure to synthesize such structures, which display remarkable N2 electrofixation activities with an ammonia yield of 72.54 µg h-1 mg-1 and a Faradic efficiency of 51.67 % that are more than three times of the FeMoS counterpart. Further mechanism studies have been conducted by density function theory (DFT) simulations. This work provides new clues for designing versatile electrocatalytic materials for large-scale industrialization.

Piezoelectric potential enhanced photocatalytic performance based on ZnO with different nanostructures.

In this paper, two novel nanostructures with ZnO nanowire and nanosheet arrays vertically growing on the FTO and Al foil have been synthesized by a hydrothermal method, which exhibit both the piezoelectric and photocatalytic properties. These nanostructures have typical wurtzite structures based on the XRD results. From the SEM results, the average diameter and length of nanowire have been measured to be about 150 nm and 4.5 µm, the thickness of ZnO nanosheet is about 50 nm and the width is about 5 µm. In the photocatalytic test, the photodegradation of RhB under 365 nm illumination for nanowire and nanosheet is about 25% and 37% in 80 min reaction. With stirring, the degradation rate is increased to 61% and 85%. Finally, the photocurrent test and finite element method were used to analyze the piezo-photodegradation mechanism.

Early neurovascular changes in the retina in preclinical diabetic retinopathy and its relation with blood glucose.

BACKGROUND: To investigate the changes in retinal nerve fiber layer thickness and macular blood flow density during the preclinical stage of diabetic retinopathy and their relationship with blood glucose. METHODS: In this cross-sectional study, 97 diabetic patients (total of 188 eyes; 144 eyes in no diabetic retinopathy group, 44 eyes in mild diabetic non-proliferative retinopathy group) and 35 healthy people (70 eyes) were enrolled, All the subjects were divided into different groups based on their HbA1c levels, and they underwent optical coherence tomography angiography. We compared the optical coherence tomography angiography parameters and retinal nerve fiber layer thickness among the different glucose groups. RESULTS: The parafoveal vessel density and the temporal retinal nerve fiber layer thickness were lower (p < 0.05) in the diabetic group than in the normal group. The diabetic group showed a higher acircularity index than the normal group. The normal group had the highest vessel density and the lowest acircularity index, followed by the no-diabetic retinopathy group and the mild non-proliferative retinopathy group, (p < 0.001). Foveal vascular density and parafoveal vessel density decreased with an increase in HbA1c. There was a negative correlation between parafoveal vessel density in the deep retinal vascular layer and fasting blood glucose (p < 0.01). The temporal retinal nerve fiber layer thickness decreased across the HbA1c level groups, and was positively correlated with the parafoveal vessel density in the superficial retinal vascular layer (p < 0.05). CONCLUSIONS: This study shows that retinal microvasculopathy and neuropathy can be present in the absence of retinopathy. The vessel density of the deep retinal vascular layer was negatively correlated with fasting blood glucose, and the temporal retinal nerve fiber layer thickness was positively correlated with the vessel density of the superficial retinal vascular layer. These indicators are helpful for endocrinologists and ophthalmologists in detecting early diabetic retinal pathological lesions.

Comparison of norepinephrine, dopamine and dobutamine combined with enteral nutrition in the treatment of elderly patients harboring sepsis.

The present study was performed in order to investigate the safety and efficacy of different vasoactive drugs combined with enteral nutrition in terms of treating elderly patients with sepsis. A total of 75 elderly patients with sepsis treated with enteral nutrition in our hospital were randomly divided into three groups: group A (n = 25), group B (n = 25) and group C (n = 25). The three groups were treated with dopamine, dobutamine and norepinephrine respectively. One week after treatment, the therapeutic effects of the three groups were compared, the vascular elastic indexes, hemodynamic indexes and levels of inflammatory factors of the three groups were measured. After treatment, the clinical effective rate of group C was evidently higher than that of group A and group B. The vascular elasticity coefficient and stiffness coefficient in group C were significantly lower than those in group A and group B, and the arterial compliance in group C was significantly higher than that in group A and group B (P < 0.05). The levels of MAP and PVRI in group C were significantly higher than those in group A and B, and the levels of CI, CVP and HR in group C were significantly lower than those in group A and group B (P < 0.05). Norepinephrine elicited greater effects in terms of improving hemodynamic indexes, vascular elasticity and reducing the level of inflammatory factors compared with dopamine and dobutamine in elderly patients harboring sepsis.

RNA-Seq revealed that infection with white tip nematodes could downregulate rice photosynthetic genes.

White-tip nematode, Aphelenchoides besseyi is a kind of widely distributed migratory parasitic nematode that can infect plant shoots. Transcriptome sequencing of plant parasitic nematodes and their host plants is helpful for understanding their interaction relationship. This study first reported expression patterns of defense-related genes in rice, and rice transcriptomes at different periods after infection with A. besseyi. The result showed that the defense response pathways of rice changed obviously in the early stage of A. besseyi infection, including upregulated salicylic acid and jasmonate pathways and a downregulated ethylene pathway. Transcriptome analysis results suggested that A. besseyi infection was associated with the downregulation of multiple genes related to photosynthesis with possible suppression of the photosynthetic activity. It suggested that the photosynthesis system of rice could be suppressed by infections of migratory nematodes, including A. besseyi and Hirschmanniella oryzae, but was stimulated by that of a sedentary nematode, Meloidogyne graminicola, by comparing our study with the reported transcriptome. OS09G0417800 (OsWRKY62) might play an important role in the interaction of migratory nematodes and rice. It also indicated that the infection strategy of both A. besseyi and the reported migratory nematode H. oryzae was similar to that of the fungal pathogen Magnaporthe grisea. These results provided an interesting starting point to elucidate the mechanism of the interaction between rice and A. besseyi, as well as the host and migratory plant nematodes.

Identification and function of FAR protein family genes from a transcriptome analysis of Aphelenchoides besseyi.

Motivation: The rice white tip nematode (RWTN) Aphelenchoides besseyi is a migratory plant parasitic nematode that infects the aboveground parts of plants. Fatty acid- and retinoid-binding (FAR) proteins are nematode-specific proteins that are involved in many important biological processes. Genes encoding FAR proteins have been identified in many species of nematodes, which indicated that nematodes may produce more than one type of FAR protein. The main goal of this study is to find new molecular targets including new far genes that will help control RWTN, and reduce the economic damage caused by RWTN. Results: Two RWTN populations with different levels of pathogenicity and reproduction were sequenced and analyzed with next-generation sequencing. 17 087 transcripts were annotated using six databases and 1696 differentially expressed genes (DEGs) were identified between the two RWTN populations. Seven new Ab-far genes were identified from the transcriptome data of the two RWTN populations which is the first to identify multiple far genes in plant parasitic nematodes. This study is the first to identify far genes in the nervous system of nematodes and the first to report a transcriptome sequencing analysis of different RWTN populations. The results help elucidate the genes related to parasitism and pathogenicity and also contribute to the identification of new target genes and development of new methods to control RWTN. Availability and implementation: Our data are publicly available at Sequence Read Archive (SRA) database and GenBank database. Supplementary information: Supplementary data are available at Bioinformatics online.

Overexpression of Forkhead box Q1 correlates with poor prognosis in papillary thyroid carcinoma.

OBJECTIVE: Forkhead box Q1 (FOXQ1), a member of the forkhead transcription factor family, plays important parts in cell cycle, apoptosis, metabolism, immunology and tumour genesis. Its expression has been associated with poor clinical prognosis in various tumours. However, the clinical significance of FOXQ1 in papillary thyroid carcinoma (PTC) has not been fully studied. The purpose of this study was to investigate whether FOXQ1 is correlated with poor prognosis in PTC. DESIGN/METHODS: We performed a retrospective study of 136 PTCs. Immunohistochemistry (IHC) was used to examine the expression of FOXQ1 in 136 PTCs and 47 nodular goitre specimens. Rank-sum test, chi-square test, Kaplan-Meier survival analysis, univariate and multivariate Cox analyses were used to investigate the clinical and prognostic significance of FOXQ1 expression in PTC. RESULTS: The comparison of PTC specimens with nodular goitre with papillary hyperplasia specimens revealed an upregulation of FOXQ1 in PTC. Overexpression of FOXQ1 was observed in 63.24% of PTC and correlated with classic variant, tall variant, distant metastasis, AJCC stage and recurrence. FOXQ1-positive expression was associated with shorter disease-free survival: median disease-free survival of FOXQ1-positive patients was 23 months compared with 128 months for FOXQ1-negative patients (Log-rank χ2  = 12.31, P = 0.00045). Additional independent risk factors in this study were multifocality (recurrence-free survival [RFS]: hazard ratio [HR] = 2.391, P < 0.05), extrathyroidal extension (RFS: HR = 3.906, P < 0.05) and positive expression of FOXQ1 (RFS: HR = 6.385, P < 0.01). CONCLUSIONS: Our results indicated that FOXQ1 may be a useful additional biomarker to evaluate the progression of PTC and to predict likely relapse of disease.

Identification and Characterization of a Fatty Acid- and Retinoid-Binding Protein Gene (Ar-far-1) from the Chrysanthemum Foliar Nematode, Aphelenchoides ritzemabosi.

The chrysanthemum foliar nematode (CFN), Aphelenchoides ritzemabosi, is a migratory, plant-parasitic nematode that is widely distributed and infects the aboveground parts of many plants. The fatty acid- and retinoid-binding proteins (FAR) are nematode-specific proteins that are involved in the development, reproduction, and infection of nematodes and are secreted into the tissues to disrupt the plant defense reaction. In this study, we obtained the full-length sequence of the FAR gene (Ar-far-1) from CFN, which is 727 bp and includes a 546 bp ORF that encodes 181 amino acids. Ar-FAR-1 from CFN has the highest sequence similarity to Ab-FAR-1 from A. besseyi, and they are located within the same branch of the phylogenetic tree. Fluorescence-based ligand-binding analysis confirmed that recombinant Ar-FAR-1 was bound to fatty acids and retinol. Ar-far-1 mRNA was expressed in the muscle layer, intestine, female genital system, and egg of CFN, and more highly expressed in females than in males among the four developmental stages of CFN. We demonstrated that the reproduction number and infection capacity of CFN decreased significantly when Ar-far-1 was effectively silenced by in vitro RNAi. Ar-far-1 plays an important role in the development, reproduction, infectivity, and pathogenesis of CFN and may be used as an effective target gene for the control of CFN. The results provide meaningful data about the parasitic and pathogenic genes of CFN to study the interaction mechanism between plant-parasitic nematodes and hosts.

Chemical Protein Synthesis Enabled Mechanistic Studies on the Molecular Recognition of K27-linked Ubiquitin Chains.

New synthetic strategies that exploited the strengths of both chemoselective ligation and recombinant protein expression were developed to prepare K27 di-ubiquitins (diUb), which enabled mechanistic studies on the molecular recognition of K27-linked Ubs by single-molecule Förster resonance energy transfer (smFRET) and X-ray crystallography. The results revealed that free K27 diUb adopted a compact conformation, whereas upon binding to UCHL3, K27 diUb was remodeled to an open conformation. The K27 isopeptide bond remained rigidly buried inside the diUb moiety during binding, an interesting unique structural feature that may explain the distinctive biological function of K27 Ub chains.

[Research progress of ellagitannin intestinal metabolite urolithins].

Ellagitannins is a kind of phenolic compounds with many biological activities. Recent studies have found that the effective ingredients of these compounds have close relationship with their colon-derived bacteria metabolites, that is urolithins. The objective of this study was to review the structure characteristics, types and distribution of urolithins, improvement in diseases related to prostate, breast and colon, as well as anti-cancer, anti-oxidation, anti-inflammation and other biological activities. The present review will lay the foundation for development and utilization of urolithins.

[Effect of Chit-oligosaccharide/Collagen Composite Gels on Pre-osteoblastic MC3T3-E1s Differentiation].

Chit-oligosaccharide(COS)is a low-molecular,water-soluble mass with higher biological activity,which can be absorbed by human body easily and interact with cells directly.Based on the excellent biological properties of collagen(Col)and COS,a series of Col and COS composite hydrogel(Col/COSn)was constructed in this study.The effect of composite hydrogel on cells proliferation,differentiation and related osteogenic gene expression was evaluated on pre-osteoblast MC3T3-E1 s.The experimental results showed that all the Col/COS composite gels could promote the growth of MC3T3-E1 s,proliferation and bone related gene expression compared to that of pure Col gels.And there was significant difference among the composite hydrogel groups with different degrees of polymerization of COS.The effect of the composite gel which contained chitotetraose(COS4)or chitohexaose(COS6)on the cells proliferation was better than that of other groups,while on cells differentiation and related osteogenic gene expression the composite gel contained chitopentaose(COS5)was the best in all the groups.