Search

Gallbladder cancer (GBC) is the most common malignant tumor in the biliary system, characterized by high malignancy, aggressiveness, and poor prognosis. Early diagnosis holds paramount importance in ameliorating therapeutic outcomes. Presently, the clinical diagnosis of GBC primarily relies on clinical-radiological-pathological approach. However, there remains a potential for missed diagnosis and misdiagnose in the realm of clinical practice. We firstly analyzed the blood-based biomarkers, such as carcinoembryonic antigen and carbohydrate antigen 19-9. Subsequently, we evaluated the diagnostic performance of various imaging modalities, including ultrasound (US), endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT) and pathological examination, emphasizing their strengths and limitations in detecting early-stage GBC. Furthermore, we explored the potential of emerging technologies, particularly artificial intelligence (AI) and liquid biopsy, to revolutionize GBC diagnosis. AI algorithms have demonstrated improved image analysis capabilities, while liquid biopsy offers the promise of non-invasive and real-time monitoring. However, the translation of these advancements into clinical practice necessitates further validation and standardization. The review highlighted the advantages and limitations of current diagnostic approaches and underscored the need for innovative strategies to enhance diagnostic accuracy of GBC. In addition, we emphasized the importance of multidisciplinary collaboration to improve early diagnosis of GBC and ultimately patient outcomes. This review endeavoured to impart fresh perspectives and insights into the early diagnosis of GBC., (Copyright © 2024 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

This study investigated the possible interaction between gut flora and miRNAs and the effect of both on anxiety disorders. The model group was induced with chronic restraint stress (CRS) and each group was tested for anxiety-like behaviour by open field test and elevated plus maze test. Meanwhile, the gut flora was analysed by 16S rRNA high-throughput sequencing. The miRNAs in hippocampus were analysed by high-throughput sequencing, and the key miRNAs were obtained by using the method of bioinformatics analysis. PCR was used to verify the significantly related key miRNAs. Spearman correlation analysis was used to explore the correlation between behaviour, key miRNAs and differential gut microbiota. The 16S rRNA high-throughput sequencing result showed that the gut flora was dysregulated in the model group. In particular, Verrucomicrobia, Akkermansia, Anaerostipes, Ralstonia, Burkholderia and Anaeroplasma were correlated with behaviour. The results of miRNA high-throughput sequencing analysis and bioinformatics analysis showed that 7 key miRNAs influenced the pathogenesis of anxiety, and qRT-PCR results were consistent with the high-throughput sequencing results. Mmu-miR-543-3p and mmu-miR-26a-5p were positively correlated with Verrucomicrobia, Akkermansia and Anaerostipes. Therefore, we infer that chronic stress caused the decrease of Akkermansia abundance, which may aggravate the decrease of mmu-miR-543-3p and mmu-miR-26a-5p expression, leading to the increase of SLC1A2 expression. In conclusion, gut flora has played an important influence on anxiety with changes in miRNAs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Evidence on the impacts of PM1, PM2.5, and PM10 on the hospital admissions, length of hospital stays (LOS), and hospital expenses among patients with cardiovascular disease (CVD) is still limited in China, especially in rural areas. This study was performed in eight counties of Fuyang from 1 January 2015 to 30 June 2017. We use a three-stage time-series analysis to explore the effects of short-term exposure to PM1, PM2.5, and PM10 on hospital admissions, LOS, and hospital expenses for CVDs. An increment of 10 ug/m3 in PM1, PM2.5, and PM10 corresponded to an increment of 1.82% (95% CI: 1.34, 2.30), 0.96% (95% CI: 0.44, 1.48), and 0.79% (95% CI: 0.63%, 0.95%) in CVD hospital admissions, respectively. We observed that daily concentrations of PMs were associated with an increase in hospital admissions, LOS, and expenses for CVDs. Sustained endeavors are required to reduce air pollution so as to attenuate disease burdens from CVDs.

Background: The industrial scale cryo-storage of raw tissue materials requires a robust, low-cost and easy-to-operate method that can facilitate the down-stream process., Objective: The study was aimed to develop the multifunctional protective solutions (MPS) for transportation at ambient conditions and also subsequent cryo-storage below -20 degree C of raw porcine hides for tissue engineering and regenerative medicine., Materials and Methods: Protective solutions with antimicrobial activity and proteinase-inhibiting activity were developed and tested for its efficacy in preserving the extracellular matrix of porcine dermis from microbial spoilage, proteolytic degradation, freeze damage and excessive dehydration during shipping and cryo-storage. The MPSs contained phosphate-buffered saline with ethylene diamine tetra acetic acid (EDTA) added as chelator and proteinase inhibitor, as well as glycerol or maltodextrin (M180) as cryoprotectants., Results: MPSs prepared with EDTA and glycerol or M180 had significant antimicrobial activity and proteinase-inhibiting activity during the period of shipping and handling. Glycerol and M180 prevented eutectic salt precipitation and excessive freeze dehydration upon cryo-storage of porcine hides. Without glycerol or M180, hides could be freeze-dehydrated to the low hydration at ~0.4 g/g dw, and formed irreversible plications after freezing. A critical hydration (0.8~0.9 g/g dw) was observed for the extracellular matrix of porcine dermis, and dehydration to a lower level could impose enormous stress and potential damage. The soaking of porcine hides in MPSs decreased water content as glycerol and M180 entered into dermis. Upon equilibration, the glycerol content in the tissue was about 94% of the incubating glycerol solution, but the M180 content in the tissue was only about 50% of the incubating M180 solution, indicating that M180 did not get into the entire aqueous domain within dermis. MPSs reduced ice formation and increased the unfrozen water content of porcine raw hides upon cryo-storage., Conclusion: MPSs prepared with EDTA and glycerol or M180 have antimicrobial activity and proteinase-inhibiting activity, which can be used for transportation and cryo-storage of raw hides at the industrial scale. Glycerol at 7.5% w/v and M180 at 20% w/v were sufficient to prevent freeze damage and excessive freeze dehydration. Doi.org/10.54680/fr24310110312.

Background: Human donor skin is processed to make the acellular dermis matrix (ADM) for tissue repair and regeneration. There is no data on the viscoelastic properties of ADM at room and subzero temperatures., Objective: The work evaluated the temperature dependence of viscoelastic properties of freeze-dried ADM., Materials and Methods: Donor skin was de-epidermized, de-cellularized and freeze-dried with trehalose as the lyo-protectant. Glass transition of freeze-dried ADM was measured by differential scanning calorimeter (DSC), and viscoelastic properties were examined by dynamic mechanical analyzer (DMA)., Results: At the low moisture range (1.4 +/- 0.5%), the glass transition temperature (Tg) of freeze-dried ADM was 90 degree C to 100 degree C. As the moisture content increased, the Tg decreased steadily. At the high moisture range (10.8 +/- 2.9%), the Tg was 40 degree C to 60 degree C. There were large donor-to-donor variations in viscoelastic properties of freeze-dried ADM as demonstrated by the changes in storage modulus (G'), loss modulus (G") and damping factor tan delta (G"/G'). However, the trends of the temperature dependence for G', G" and tan delta were similar among all 8 donors. For each donor, changes in G' and G" were relatively small between -90 degree C and 40 degree C, and G' was at least one order of magnitude greater than G". Two viscoelastic relaxations were observed in freeze-dried ADM, one at -20 degree C and the other at -60 degree C respectively., Conclusion: Freeze-dried ADM was protected in the glassy carbohydrate matrix. DMA observed two viscoelastic relaxations (i.e., alpha process at -20 degree C and beta process at -60 degree C). Overall changes in G' and G'' of freeze-dried ADM were relatively small within one order of magnitude between -90 degree C and 40 degree C. https://doi.org/10.54680/fr24110110612.

Allogenic demineralized bone matrix (DBM), processed to expose bioactive proteins imbedded by calcium salts, is widely used for bone repair and regeneration as an alternative to the autologous bone graft. However, demineralized bone matrices from tissue banks vary significantly in residual calcium content and osteogenicity for clinical bone regeneration. The present study produced DBM with various residual calcium contents by partial demineralization using ethylenediaminetetraacetic acid disodium (EDTA) and hydrochloric acid. Compositional analysis reveals that, as the percent weight loss of bone materials increases from 0% to 74.9% during demineralization, the residual calcium content of DBM decreases from 24.8% to 0.2% and collagen content increases from 29.7% to 92.6%. Calorimetrical analysis and Fourier transform infrared (FTIR) analysis demonstrated that demineralization to the residual calcium content of <4% enables the complete exposure and/or release of bone collagen fibers and other bioactive molecules. In order to evaluate the relationship between the extent of demineralization and the osteogenicity of DBM, DBM particles were fabricated with the aid of acellular dermal matrix (ADM) microfibers to form flexible foam-like DBM/ADM composites. Proteomic analysis identified various type collagens and bone formation-related bioactive molecules in both ADM and DBM. Using the rat bilateral Φ = 5 mm calvarium defect repair model, the study had shown that the DBM/ADM composite with ~20% DBM residual calcium (e.g., ~40% calcium being removed) maximized the osteogenicity for bone defect repair after 4 and 8 weeks. DBM with ~40% calcium removal had the maximal osteogenicity presumably through the sustained release of bioactive molecules during the process of bone regeneration., (© 2023 Wiley Periodicals LLC.)

Acellular tissue matrices are used in regenerative medicine from weak tissue re-enforcement to cosmetic augmentation. However, proteomic signatures leading to different clinical outcomes among matrices are not well understood. In an attempt to investigate the effects of tissue source and processing method, we examined by liquid chromatography tandem mass spectrometry (LC-MS/MS) the proteomic profiles of 12 regulatory agency-approved acellular matrices (AlloMax, AlloDerm, CollaMend, Heal-All, JayyaLife, ReGen, Renov, Strattice, SurgiMend, Surgisis, UniTrump and Vidasis). The compositions of acellular matrices varied greatly with the number of identified proteins ranging from 7 to 106. The content of individual proteins was between 0.0001% and 95.8% according to their abundances measured by the M/Z signal intensities. Most acellular matrices still contained numerous cellular proteins. AlloMax, AlloDerm, ReGen, Strattice, SurgiMend and Surgisis retained necessary structural and functional proteins to form the extracellular protein-protein interaction networks for cell adhesion, proliferation and tissue regeneration, whereas CollaMend, Heal-All, JayyaLife, Renov, UniTrump and Vidasis had only retained certain structural collagens. Principal component analysis showed that proteomic variations among acellular matrices were largely attributed to tissue source and processing method. Differences in proteomic profiles among acellular matrices offers insights into molecular interpretation for different clinical outcomes, and can serve as useful references for rational design of regenerative bio-scaffolds., (© 2023 Wiley Periodicals LLC.)

Thyroid cancer, a common endocrine malignancy, is one of the leading death causes among endocrine tumors. The diagnosis of pathological section analysis suffers from diagnostic delay and cumbersome operating procedures. Therefore, we intend to construct the models based on spectral data that can be potentially used for rapid intraoperative papillary thyroid carcinoma (PTC) diagnosis and characterize PTC characteristics. To alleviate any concerns pathologists may have about using the model, we conducted an analysis of the used bands that can be interpreted pathologically. A spectra acquisition system was first built to acquire spectra of pathological section images from 91 patients. The obtained spectral dataset contains 217 spectra of normal thyroid tissue and 217 spectra of PTC tissue. Clinical data of the corresponding patients were collected for subsequent model interpretability analysis. The experiment has been approved by the Ethics Review Committee of the Wuhu Hospital of East China Normal University. The spectral preprocessing method was used to process the spectra, and the preprocessed signal respectively optimized by the first and secondary informative wavelengths selection was used to develop the PTC detection models. The PTC detection model using mean centering (MC) and multiple scattering correction (MSC) has optimal performance, and the reasons for the good performance were analyzed in combination with the spectral acquisition process and composition of the test slide. For model interpretable analysis, the near-ultraviolet band selected for modeling corresponds to the location of amino acid absorption peak, and this is consistent with the clinical phenomenon of significantly lower amino acid concentrations in PTC patients. Moreover, the absorption peak of hemoglobin selected for modeling is consistent with the low hemoglobin index in PTC patients. In addition, the correlation analysis was performed between the selected wavelengths and the clinical data, and the results show: the reflection intensity of selected wavelengths in normal cells has a moderate correlation with cell arrangement structure, nucleus size and free thyroxine (FT4), and has a strong correlation with triiodothyronine (T3); the reflection intensity of selected bands in PTC cells has a moderate correlation with free triiodothyronine (FT3)., Competing Interests: Conflict of InterestThe authors declare that they have no competing interests., (© International Human Phenome Institutes (Shanghai) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Semen cryopreservation is a promising technology employed in preserving high-quality varieties in animal husbandry and is also widely applied in the human sperm bank. However, the compromised qualities, such as decreased sperm motility, damaged membrane structure, and reduced fertilization competency, have significantly hampered the efficient application of this technique. Therefore, it is imperative to depict various molecular changes found in cryopreserved sperm and identify the regulatory network in response to the cryopreservation stress. In this study, semen was collected from three Chinese Merino rams and divided into untreated (fresh semen, FS) and programmed freezing (programmed freezing semen, PS) groups. After measuring different quality parameters, the ultra-low RNA-seq and tandem mass tag-based (TMT) proteome were conducted in both the groups. The results indicated that the motility (82.63% ± 3.55% vs. 34.10% ± 2.90%, p < 0.05) and viability (89.46% ± 2.53% vs. 44.78% ± 2.29%, p < 0.05) of the sperm in the FS group were significantly higher compared to those in the PS group. In addition, 45 upregulated and 291 downregulated genes, as well as 30 upregulated and 48 downregulated proteins, were found in transcriptomics and proteomics data separately. Moreover, three integrated methods, namely, functional annotation and enrichment analysis, Pearson's correlation analysis, and two-way orthogonal partial least squares (O2PLS) analysis, were used for further analysis. The results suggested that various differentially expressed genes and proteins (DEGs and DEPs) were mainly enriched in leishmaniasis and hematopoietic cell lineage, and Fc gamma receptor Ia (FCGR1A) was significantly downregulated in cryopreserved sperm both at mRNA and protein levels in comparison with the fresh counterpart. In addition, top five genes ( FCGR1A , HCK , SLX4 , ITGA3 , and BET1 ) and 22 proteins could form a distinct network in which genes and proteins were significantly correlated ( p < 0.05). Interestingly, FCGR1A also appeared in the top 25 correlation list based on O2PLS analysis. Hence, FCGR1A was selected as the most potential differentially expressed candidate for screening by the three integrated multi-omics analysis methods. In addition, Pearson's correlation analysis indicated that the expression level of FCGR1A was positively correlated with sperm motility and viability. A subsequent experiment was conducted to identify the biological role of FCGR1A in sperm function. The results showed that both the sperm viability (fresh group: 87.65% ± 4.17% vs. 75.8% ± 1.15%, cryopreserved group: 48.15% ± 0.63% vs. 42.45% ± 2.61%, p < 0.05) and motility (fresh group: 83.27% ± 4.15% vs. 70.41% ± 1.07%, cryopreserved group: 45.31% ± 3.28% vs. 35.13% ± 2.82%, p < 0.05) were significantly reduced in fresh and frozen sperm when FCGR1A was blocked. Moreover, the cleavage rate of embryos fertilized by FCGR1A-blocked sperm was noted to be significantly lower in both fresh (95.28% ± 1.16% vs. 90.44% ± 1.56%, p < 0.05) and frozen groups (89.8% ± 1.50% vs. 82.53% ± 1.53%, p < 0.05). In conclusion, our results revealed that the downregulated membrane protein FCGR1A can potentially contribute to the reduced sperm fertility competency in the cryopreserved sheep sperm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor KC declared a past co-authorship with the authors JL and XF., (Copyright © 2023 Bai, Zhou, Hao, Liu, Guo, Wang, Liu, Wang, Li, Liu, Sun, Wan and Fu.)

Background: The cognitive benefits of early non-pharmacological approaches have been demonstrated in older adults with mild cognitive impairment (MCI). However, older adults living in nursing homes have more severe cognitive impairment problems and lower initiative and compliance to participate in complex interventions. Hence, it important to investigate more attractive and sustainable methods to prevent or delay cognitive decline. The present study adopts the self-determination theory (SDT) as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes in China and aims to evaluate its effects on cognitive function, mental health, and other health-related outcomes., Methods: The study is a nursing home-based, cluster randomised controlled trial (RCT) that targets older adults (aged ≥ 60 years) with MCI in Fuzhou City, China. All nursing homes in the area covered by Fuzhou City are invited to participate. Eligible nursing homes are randomised to one of two groups: intervention group (receive a 14-week, 27-session intervention) and waitlist control group (receive the usual care). The SDT-based integrated creative art (SDTICA) program reasonably adopts the SDT as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes. The primary (global cognitive function and psychological indicator) and secondary (daily activity function, social function, and specific domains of cognitive function) outcomes will be measured at baseline, after the intervention, and during follow-up., Discussion: This study aims to evaluate the effects of SDTICA program on neuropsychological outcomes in older adults with MCI and provide scientific evidence for art-based non-pharmacologic interventions in nursing homes, which may reduce dementia risk in older adults with MCI., Trial Registration: The trial was prospectively registered at the Chinese Clinical Trials Registry with the registration number ChiCTR2200061681 on 30 June 2022., (© 2023. The Author(s).)

Background: It was demonstrated that external stress, such as in vitro maturation (IVM) and vitrification process can induce significantly reduced development capacity in oocytes. Previous studies indicated that antioxidants play a pivotal part in the acquisition of adaptation in changed conditions. At present, the role of the natural potent antioxidant PCB2 in response to IVM and vitrification during ovine oocyte manipulation has not been explored., Objective: To investigate whether PCB2 treatment could improve the developmental potential of ovine oocytes under IVM and vitrification stimuli., Materials and Methods: The experiment was divided into two parts. Firstly, the effect of PCB2 on the development of oocytes during IVM was evaluated. Un-supplemented and 5 ug per mL PCB2-supplemented in the IVM solution were considered as control and experimental groups (C + 5 ug per mL PCB2). The polar body extrusion (PBE) rate, mitochondrial membrane potential (MMP), ATP, reactive oxygen species (ROS) levels and early apoptosis of oocytes were measured after IVM. Secondly, we further determine whether PCB2 could improve oocyte quality under vitrification stress. The survival rate, PBE rate and early apoptosis of oocytes were compared between fresh group, vitrified group and 5 ug per mL PCB2-supplemented in the IVM solution after vitrification (V + 5 ug per mL PCB2)., Results: Compared to the control group, adding PCB2 significantly increased PBE rate (79.4% vs. 62.8%, P < 0.01) and MMP level (1.9 +/- 0.08 vs. 1.3 +/- 0.04, P < 0.01), and decreased ROS level (47.1 +/- 6.3 vs. 145.3 +/- 8.9, P < 0.01). However, there was no significant difference in ATP content and early apoptosis. Compared to the fresh group, vitrification significantly reduced oocytes viability (43.0% vs. 90.8%, P < 0.01) as well as PBE rate (24.2% vs. 60.6%, P < 0.05). However, 5 ug per mL PCB2-supplemention during maturation had no effect on survival, PBE or early apoptosis in vitrified oocytes., Conclusion: PCB2 could effectively antagonise the oxidative stress during IVM and promote oocyte development. DOI: 10.54680/fr23210110412.

Much effort has been devoted to the development of supramolecular hydrogels due to their broad applications and conveniently controllable properties. Here, we demonstrate a novel supramolecular host - guest hydrogel, which is constructed by the host γ-CD complexed with the guest 1-(4-carboxybenzyl)-4,4'-bipyridinium chloride ( 1 + ·Cl - ) through the π···π interaction, hydrogen bonding, and host-guest interactions. The supramolecular hydrogel [ 1 + @γ-CD] n exhibits reversible electron transfer photochromic behavior and photomodulable fluorescence. The excellent photochromic and fluorescence properties support the practical utility of the supramolecular hydrogel as a visual display and anti-counterfeiting material.

Regenerative bio-scaffolds, widely used for clinical tissue reconstruction and tissue repairs, are functionally diversified and structurally complex decellularized tissue materials (e.g., extracellular matrix, ECM). ECM is naturally cross-linked and can be further selectively cross-linked upon processing. Identification, quantification and bioinformatics functional comparison of all ECM proteins are challenging for regenerative bio-scaffolds. In this study, we have applied proteomic profiling with a two-step sequential trypsinization method, and identified and quantified 300-400 constituent proteins in three commercially available regenerative bio-scaffolds (BioDesign Surgisis, ReGen tissue matrix, and ThormalGEN mesh). These proteins were classified into four categories and 14 subcategories based on their mainly biological function. The main components of regenerative bio-scaffolds were highly abundant ECM structural proteins, and the minor parts of bio-scaffolds were lowly abundant, less cross-linked, functionally more diversified proteins, especially extracellular fluid proteins that were easily solubilized by trypsin. The comparative analysis has revealed large differences in the number, type, abundance and function of identified proteins, as well as the extent of decellularization and cross-linking among regenerative bio-scaffolds. So, the proteomic profiling with a two-step sequential trypsinization method could not only provide the molecular basis to better understand the degradation process of regenerative bio-scaffolds in vivo and different clinical outcomes among various regenerative bio-scaffolds, facilitate the exploration of the response mechanisms in the host's early clinical stages of ECM-induced tissue regeneration that is still poorly understood, but also can be used for optimization of the decellularization and cross-linking process, product characterization and rational design of new ECM products., (© 2022 Wiley Periodicals LLC.)

Background: The brown adipose tissue (BAT) is a target for treating obesity. BAT losses thermogenic capacity and gains a "white adipose tissue-like" phenotype ("BAT whitening") under thermoneutral environments, which is a potential factor causing a low curative effect in BAT-related obesity treatments. Circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNA) to mRNAs and function in various processes by sponging shared microRNAs (miRNAs). However, the roles of circRNA- and lncRNA-related ceRNA networks in regulating BAT whitening remain litter known., Results: In this study, BATs were collected from rabbits at day0 (D0), D15, D85, and 2 years (Y2). MiRNA-seq was performed to investigate miRNA changes during BAT whitening. Then, a combined analysis of circRNA-seq and whole-transcriptome sequencing was used for circRNA assembly and quantification during BAT whitening. Our data showed that 1187 miRNAs and 6204 circRNAs were expressed in the samples, and many of which were identified as significantly changed during BAT whitening. Target prediction showed that D0-selective miRNAs were significantly enriched in the Ras, MAPK, and PI3K-Akt signaling pathways, and Y2-selective miRNAs were predicted to be involved in cell proliferation. The cyclization of several circRNAs could form novel response elements of key thermogenesis miRNAs at the back-splicing junction (BSJ) sites, and in combination with a dual-luciferase reporter assay confirmed the binding between the BSJ site of novel&#95;circ&#95;0013792 and ocu-miR-378-5p. CircRNAs and lncRNAs have high cooperativity in sponging miRNAs during BAT whitening. Both circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA triple networks were significantly involved in immune response-associated biological processes. The D15-selective circRNA might promote BAT whitening by increasing the expression of IDH2. The Y2-selective circRNA-related ceRNA network and lncRNA-related ceRNA network might regulate the formation of the WAT-like phenotype of BAT via MAPK and Ras signaling pathways, respectively., Conclusions: Our work systematically revealed ceRNA networks during BAT whitening in rabbits and might provide new insight into BAT-based obesity treatments., (© 2022. The Author(s).)

An easily prepared fluoro-functionalized ionic covalent organic framework (F-iCOF) has been implemented into MALDI-TOF MS, enabling the highly selective enrichment and sensitive determination of perfluorinated sulfonate (PFS) contaminants in a rapid and convenient manner. The good thermal stability and excellent optical absorption properties of F-iCOF makes it a brilliant matrix with no background noise. Moreover, benefitting from the large surface area, appropriate pore size, good water dispersibility, and abundant fluorine atom and cationic characteristic of F-iCOF, it exhibited superior adsorption capacity and enrichment selectivity towards PFSs. Good signal responses for PFSs were obtained in the presence of various interfering compounds such as BSA, HA, or even more than 100-fold excess of glutamic acid and similar in structure sodium alkyl sulfonates, highlighting the specific selectivity of F-iCOF. Calibration curves for potassium perflurobutane sulfonate (PFBSK) in tap water and whole blood were established with good linear correlation in the range 1-500 pg mL -1 . The limits of detection and quantification for PFBSK were as low as 0.04 pg mL -1 and 0.05 pg mL -1 , respectively, which are comparable or better than the existing methods for the determination of PFSs., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

In order to investigate the photochromic mechanism of photochromic materials based on supramolecular host-guest systems, we designed and synthesized a unique viologen derivative (benzimidazolyl benzyl viologen, guest 1·Cl 3 ), which does not contain oxygen atoms. The binding interaction of guest 1 3+ with host cucurbit[7]uril (Q[7]) was investigated by various techniques. The obtained supramolecular host-guest complex 1 3+ @Q[7] exhibits interesting fluorescence emission and reversible photochromism. The ESR and XPS experimental data suggest that the photochromic process of the complex 1 3+ @Q[7] comes from the electron transfer from the carbonyl O atoms of the host Q[7] to the bipyridinium N atoms of the guest 1 3+ .

DNA methylation alters gene expression in numerous biological processes, including embryonic development. It is little known about the effect of cryopreservation on sperm DNA methylation. The present study has investigated whether cryopreservation causes abnormal DNA methylation in cynomolgus macaque sperm for five critical genes that includes the maternally imprinted gene (SNRPN), genes associated with male infertility (HSPA1L, MTHFR) and genes involved in embryonic development (TET3, LZTR1). Our results showed that sperm motility, the percentage of acrosomal integrity, DNA integrity and mitochondrial membrane potential were decreased after cryopreservation either being frozen with penetrating cryoprotectant, glycerol (Gly) or ethylene glycol (EG), compared to fresh sperm (p = 0.000), but the methylation patterns of the five target genes from cynomolgus macaque sperm samples were not affected after cryopreservation as evaluated by the Bisulfite Sequencing PCR (BSP) method. The data indicates that the current protocol for sperm cryopreservation of cynomolgus macaque is safe in terms of DNA methylation levels in these genes related to critical sperm functions., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier Inc.)

Background: Developmental stage and cryopreservation method have significant impact on the pregnancy rate after transfer of embryos produced in vivo., Objective: To determine the pregnancy outcomes from ovine embryos cryopreserved at different developmental stages., Materials and Methods: Embryos at different developmental stages were obtained from donor ewes through simultaneous estrus treatment and laparoscopic artificial insemination. Embryos, either cryopreserved via vitrification or slow freezing method, were implanted into recipient ewes. The pregnancy rate was determined 35 days after transfer., Results: The pregnancy rate of developing embryos increases after transfer from the morula stage, early blastocyst to expanded blastocyst stages (64.9%, 73.9% and 81.3%, respectively). However, cryopreservation significantly decreases the pregnancy rate of embryos at all three developmental stages, and there is no significant difference among developmental stages (43.9%, 43.7%, 52.9%, respectively). There is also no significant difference in the pregnancy rate between slowly-frozen embryos and vitrified embryos., Conclusion: The pregnancy outcomes of embryo transfer is better at the expanded blastocyst stage than at earlier stages. However, no difference is observed in the pregnancy rate of embryos at different developmental stage after cryopreservation, either by slow freezing and vitrification. Cryopreservation methods for ovine embryos, both slow freezing and vitrification, need further improvement. doi.org/10.54680/fr22510110512.

Polymers have an excellent effect in terms of moderating fast neutrons with rich hydrogen and carbon, which plays an indispensable role in shielding devices. As the shielding of neutrons is typically accompanied by the generation of γ-rays, shielding materials are developed from monomers to multi-component composites, multi-layer structures, and even complex structures. In this paper, based on the typical multilayer structure, the integrated design of the shield component structure and the preparation and performance evaluation of the materials is carried out based on the design sample of the heat-resistant lightweight polymer-based interlayer. Through calculation, the component structure of the polymer-based materials and the three-layer thickness of the shield are obtained. The mass fraction of boron carbide accounts for 11% of the polymer-based material. Since the polymer-based material is the weak link of heat resistance of the multilayer shield, in terms of material selection and modification, the B 4 C/TiO 2 /polyimide molded plate was prepared by the hot-pressing method, and characterization analysis was conducted for its structure and properties. The results show that the ball milling method can mix the materials well and realize the uniform dispersion of B 4 C and TiO 2 in the polyimide matrices. Boron carbide particles are evenly distributed in the material. Except for Ti, the other elemental content of the selected areas for mapping is in good agreement with the theoretical values of the elemental content of the system. The prepared B 4 C/TiO 2 /polyimide molded plate presents excellent thermal properties, and its glass transition temperature and initial thermal decomposition temperature are as high as 363.6 °C and 572.8 °C, respectively. In addition, the molded plate has good toughness performs well in compression resistance, shock resistance, and thermal aging resistance, which allows it to be used for a long time under 300 °C. Finally, the prepared materials are tested experimentally on an americium beryllium neutron source. The experimental results match the simulation results well.

By using 1 H NMR, ESI-MS and UV spectra, a novel light-responsive molecular switch constructed using 1,1'-bis(benzyl)-4-[2-(4-pyridyl)-vinyl]-pyridinium (1 2+ ) and cucurbit[7]uril (Q[7]) is demonstrated. The E - to Z -isomerization of the double bond in 1 2+ results in the transition of the switching states from the 1 : 2 complex E -1 2+ @Q[7] 2 to the stable 1 : 1 complex Z -1 2+ @Q[7]. In particular, both the 1 : 2 complex and the 1 : 1 complex can emit cold white fluorescence under UV light.

Heat stress not only affects the physical condition but also affects reproductive performance in sheep. A thorough understanding of the molecular and physiological mechanisms underlying heat stress would certainly improve livestock productivity and provide genetic evaluation ways for heat resistant breeds selection. In this study, 85 Turpan Black sheep, a breed exhibited excellent heat resistance from long-term artificial selection, and 85 heat sensitive Kazakh sheep in Turpan basin were tested for physiological and reproductive performance from July to August in summer. The results showed that the estrus rate was significantly higher in Turpan Black sheep (P < 0.05), while the heart rate and respiratory rate of Turpan Black sheep are significantly lower than that of Kazakh sheep (P < 0.05). Furthermore, to clarify genes participated in heat stress response, the pituitary, ovarian and hepatic tissues from three Turpan Black sheep and three Kazakh sheep were subjected to RNA-seq. The results indicated that 32, 49 and 69 genes were up-regulated, and 39, 60 and 145 genes were down-regulated in pituitary, ovarian and hepatic tissues in Turpan Black sheep compared with that of the Kazakh sheep, respectively. KEGG and gene set enrichment analysis showed that the differentially expressed genes were mainly involved in signal transduction pathways. In particular, the differentially expressed genes in hepar were enriched in the energy metabolism pathway, while the differentially expressed genes in ovarian tissue were enriched in the ovarium steroidogenesis pathway. In conclusion, our results implied that the pituitary-ovary axis might include hepar as downstream targeted organism in heat resistant regulation. Under heat stress, the signals released from pituitary would impact steroidogenesis in ovary, and further alter energy metabolism in hepar. As we know, this is the first comparative study to investigate the gene expression in multi-tissue in sheep under heat stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this research, a high-boron-content composite material with both neutron and γ rays shielding properties was developed by an optimized design and manufacture. It consists of 304 stainless steel as the matrix and spherical boron carbide (B 4 C) particles as the functional particles. The content of B 4 C is 24.68 wt%, and the particles' radius is 1.53 mm. The density of the newly designed material is 5.17 g·cm -3 , about 68.02% of that of traditional borated stainless steel containing 1.7 wt% boron, while its neutrons shielding performance is much better. Firstly, focusing on shielding properties and material density, the content and the size of B 4 C were optimized by the Genetic Algorithm (GA) program combined with the MCNP program. Then, some samples of the material were manufactured by the infiltration casting technique according to the optimized results. The actual density of the samples was 5.21 g cm -3 . In addition, the neutron and γ rays shielding performance of the samples and borated stainless steel containing 1.7 wt% boron was tested by using an 241 Am-Be neutron source and 60 Co and 137 Cs γ rays sources, respectively, and the results were compared. It can be concluded that the new designed material could be used as a material for nuclear power plants or spent-fuel storage and transportation containers with high requirements for mobility.

Antifreeze protein III (AFP III) is used for the cryopreservation of germ cells in various animal species. However, the exact mechanism of its cryoprotection is largely unknown at the molecular level. In this study, we investigated the motility, acrosomal integrity, and mitochondrial membrane potential (MMP), as well as proteomic change, of cynomolgus macaque sperm after cryopreservation. Sperm motility, acrosomal integrity, and MMP were lower after cryopreservation ( p < 0.001), but significant differences in sperm motility and MMP were observed between the AFP-treated sperm sample (Cryo+AFP) and the non-treated sample (Cryo-AFP) ( p < 0.01). A total of 141 and 32 differentially expressed proteins were, respectively, identified in cynomolgus macaque sperm cryopreserved without and with 0.1 μg/ml AFP III compared with fresh sperm. These proteins were mainly involved in the mitochondrial production of reactive oxygen species (ROS), glutathione (GSH) synthesis, and cell apoptosis. The addition of AFP III in the sperm freezing medium resulted in significant stabilization of cellular molecular functions and/or biological processes in sperm, as illustrated by the extent of proteomic changes after freezing and thawing. According to the proteomic change of differentially expressed proteins, we hypothesized a novel molecular mechanism for cryoprotection that AFP III may reduce the release of cytochrome c and thereby reduce sperm apoptosis by modulating the production of ROS in mitochondria. The molecular mechanism that AFP III acts with sperm proteins for cellular protection against cryoinjuries needs further study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Wang, Inglis, Ding, Suo, Qiu, Duan, Li, Li, Sun and Si.)

Acellular Dermal Matrix (ADM) is mainly made with human or porcine skins and has the risk of zoonotic virus transmission. The fish skin-derived ADM could overcome the shortcoming. Fish skin acellular matrix has been used as wound dressing, but there is few systematic studies on tilapia-skin acellular dermal matrix (TS-ADM). In the present study, a novel TS-ADM was made by an alkaline decellularization process and γ-irradiation. The physical properties, biocompatibility, pre-clinical safety and wound healing activity of TS-ADM were systematically evaluated for its value as a functionally bioactive wound dressing. Histopathological analysis (hematoxylin and eosin staining, 4,6-diamidino-2-phenylindole (DAPI) staining) and DNA quantification both proved that the nuclear components of tilapia skin were removed sufficiently in TS-ADM. Compared to the commercial porcine acellular dermal matrix (DC-ADM), TS-ADM has distinctive features in morphology, thermal stability, degradability and water vapor transmission. TS-ADM was more readily degradable than DC-ADM in vitro and in vivo. In both rat and mini-pig skin wound healing experiments, TS-ADM was shown to significantly promote granulation growth, collagen deposition, angiogenesis and re-epithelialization, which may be attributed to the high expression of transforming growth factor-beta 1 (TGF-β1), alpha-smooth muscle actin (α-SMA) and CD31. Herein, the novel TS-ADM, used as a low-cost bioactive dressing, could form a microenvironment conducive to wound healing., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Due to the strong background interferences in the low-mass region and poor reproducibility of conventional organic matrices, it is of great importance to develop a novel matrix for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to qualitatively and quantitatively analyze small molecules. In this work, water-soluble fullerenol C 60 (OH) 24-26 was selected as a MALDI matrix for the analysis of low-molecular-weight compounds in consideration of optical absorption property, water solubility and stability. Compared with the traditional matrices, fullerenol demonstrated lower background interference and stronger peak intensity. In addition, the hydrophilic fullerenol could avoid the heterogeneous crystallization in sample preparation, increase the reproducibility and sensitivity of MALDI-MS, and ameliorate quantitative analysis of small molecules. With saccharin as model analyte, quantitative analysis was carried out using fullerenol as matrix. The results demonstrated satisfying reproducibility and good tolerance to salt. The limit-of-detection of the quantitative analysis was as low as 4 pmol, and the linear range is 1-100 μg mL -1 with R 2 greater than 0.99. The analytical results also showed excellent precision and accuracy, low matrix effect and good recovery rate. Fullerenol as a potential matrix was further validated in the quantification of saccharin sodium in different real food samples, such as nuts and drinks. This work not only confirms the potential of fullerenol for the quantitative analysis in food field, but also provides a new technique for rapid analysis of small molecules., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Worldwide women are increasingly facing the issue of delayed child-bearing and fertility decline. Oocyte cryopreservation provides an option for fertility preservation, especially for women with diseases and other special needs to conceive babies later. In this review we examine the effect of oocyte cryopreservation on early development of human embryos. Databases (Medline, PubMed and Web of Science) were searched for relevant clinical studies published between 1999 and 2020. A total of 27 studies on oocyte cryopreservation and embryo development were identified, and data in those studies are retrieved for meta-analysis on the outcomes of oocyte survival, fertilization and early embryo development. In comparison to the slow freezing technique, vitrification yields significantly better oocyte survival (84.7% ± 0.6% vs 58.0% ± 0.5%), and subsequently higher rates of fertilization (65.5% ± 0.9% vs 40.0% ± 0.6%), cleavage (58.8% ± 0.9% vs 34.6% ± 0.8%), as well as embryo implantation (5.9% ± 0.3% vs 2.9% ± 0.2%). This analysis reveals a negative 'carryover' effect of oocyte cryopreservation on early development of embryos after oocyte fertilization (i.e., cleavage and implantation). This 'carryover' effect is greater for slowly-frozen oocytes than for vitrified oocytes, and may represent subtle functional or molecular alterations that are not severe enough to affect cell survival and fertilization, but sufficient to impair later development. The nature of the 'carryover' effect is unknown. Hypothermia, membrane ion channels, bioenergy metabolism and epigenetic modifications are likely involved. In conclusion, oocyte cryopreservation can negatively affect early development of human embryos. Future studies should go beyond oocyte survival and look further into the effects on epigenetic changes.

Background: Endometriosis (EM) is a benign gynecological disease that shares some characteristics with malignancy, such as proliferation and invasion. So far, the pathogenesis of EM is still unclear. In this study, we investigated whether TRIM65 can play a role in the development of EM., Methods: TRIM65 expression levels in eutopic, ectopic, and normal endometrium were detected by quantitative real-time PCR and Western blot. Cell proliferation and invasion of primary endometrial stromal (EMS) cells were detected by CCK-8 and Transwell analysis. The interaction between TRIM65 and DUSP6 or C-myc was measured by coimmunoprecipitation, ubiquitylation, dual luciferase, and chromatin immunoprecipitation analysis., Results: We found that TRIM65 was identified as an up-regulated gene in ectopic endometrial tissues and EMS cells compared with control groups without EM. TRIM65 expression was positively correlated with the levels of p-ERK1/2, C-myc, matrix metalloproteinase-2, and integrin β1 in ectopic endometrial tissues in patients and mice. TRIM65 promoted the cell proliferation and invasion of EMS cells via the ERK1/2/C-myc pathway through ubiquitination of DUSP6. C-myc promoted TRIM65 expression through inducing TRIM65 promoter activity. Additionally, the increased expression of TRIM65, C-myc, matrix metalloproteinase-2, integrin β1, and p-ERK1/2 and the decreased expression of DUSP6 in ectopic endometrial tissues were significantly suppressed by inhibition of ERK1/2 signaling pathway in ectopic endometrial tissues in experimental mice model., Conclusion: In conclusion, TRIM65 promotes invasion of ectopic EMS cells by activating a feedback loop with the ERK1/2/C-myc signaling pathway and may be a potential therapeutic target for EM., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The development of freezing and freeze-drying processes for biological samples requires knowledge of the thermophysical properties of the biomaterial and protectant solutions involved. This chapter provides an introduction on the use of differential scanning calorimetry (DSC) to study thermophysical properties of biomaterials in protective solutions. It covers specific methods to study thermal events related to freezing and drying processes including crystallization, eutectic formation, glass transition, devitrification, recrystallization, melting, molecular relaxation, and phase separation.

Phytase has long been used to decrease the inorganic phosphorus (Pi) input in poultry diet. The current study was conducted to investigate the effects of Pi supplementation on laying performance, egg quality and phosphate-calcium metabolism in Hy-Line Brown laying hens fed phytase. Layers (n = 504, 29 weeks old) were randomly assigned to seven treatments with six replicates of 12 birds. The corn-soybean meal-based diet contained 0.12% non-phytate phosphorus (nPP), 3.8% calcium, 2415 IU/kg vitamin D3 and 2000 FTU/kg phytase. Inorganic phosphorus (in the form of mono-dicalcium phosphate) was added into the basal diet to construct seven experimental diets; the final dietary nPP levels were 0.12%, 0.17%, 0.22%, 0.27%, 0.32%, 0.37% and 0.42%. The feeding trial lasted 12 weeks (hens from 29 to 40 weeks of age). Laying performance (housed laying rate, egg weight, egg mass, daily feed intake and feed conversion ratio) was weekly calculated. Egg quality (egg shape index, shell strength, shell thickness, albumen height, yolk colour and Haugh units), serum parameters (calcium, phosphorus, parathyroid hormone, calcitonin and 1,25-dihydroxyvitamin D), tibia quality (breaking strength, and calcium, phosphorus and ash contents), intestinal gene expression (type IIb sodium-dependent phosphate cotransporter, NaPi-IIb) and phosphorus excretion were determined at the end of the trial. No differences were observed on laying performance, egg quality, serum parameters and tibia quality. Hens fed 0.17% nPP had increased (P < 0.01) duodenum NaPi-IIb expression compared to all other treatments. Phosphorus excretion linearly increased with an increase in dietary nPP (phosphorus excretion = 1.7916 × nPP + 0.2157; R2 = 0.9609, P = 0.001). In conclusion, corn-soybean meal-based diets containing 0.12% nPP, 3.8% calcium, 2415 IU/kg vitamin D3 and 2000 FTU/kg phytase would meet the requirements for egg production in Hy-Line Brown laying hens (29 to 40 weeks of age).

Sal-like protein 4 (SALL4) is overexpressed in breast cancer and might contribute to breast cancer progression, but the molecular mechanism remains unknown. Here, we found that within a group of 371 ethnic Chinese breast cancer patients, SALL4 was associated with lower grade (P = .002) and progesterone receptor positivity (P = .004) for overall cases; lower Ki67 (P = .045) and high vimentin (P = .007) for luminal cases. Patients with high SALL4 expression in lymph node metastasis showed a significantly worse survival than those with low expression. Knockout of SALL4 in a triple-negative breast cancer cell line MDA-MB-231-Red-FLuc-GFP led to suppressed ability in proliferation, clonogenic formation, migration, and mammosphere formation in vitro, tumorigenicity and lung colonization in vivo. On the other hand, overexpression of SALL4 enhanced migration and mammosphere formation in vitro and tumorigenicity in vivo. Mechanistically, there was a positive correlation between SALL4 expression and mesenchymal markers including Zinc finger E-box binding homeobox 1 (ZEB1), vimentin, Slug, and Snail in vivo. Chromatin immunoprecipitation experiment indicated that SALL4 can bind to the promoter region of vimentin (-778 to -550 bp). Taken together, we hypothesize that SALL4 promotes tumor progression in breast cancer by inducing the mesenchymal markers like vimentin through directly binding to its promoter. Increased SALL4 level in metastatic lymph node relative to the primary site is an important poor survival marker in breast cancer., (© 2020 Wiley Periodicals LLC.)

Organ transplantation is the gold standard treatment for end-stage organ failure. Due to the severe shortage of transplantable organs, only a tiny fraction of patients may receive timely organ transplantation every year. Decellularization-recellularization technology using allogeneic and xenogeneic organs is currently conceived to be a promising solution to generate functionally transplantable organs in vitro. This approach, however, still faces tremendous technological challenges, one of them being the ability to evaluate and preserve the integrity of vascular architectures upon decellularization and cryostorage of the whole organ matrices so that the off-the-shelf organ grafts are available on demand for clinical applications. In the present study, we report a Micro-CT imaging method for evaluating the integrity of vasculature of the decellularized whole organ scaffolds with/without freezing/thawing. The method uses radiopaque Microfil perfusion and x-ray fluoroscopy to acquire high-resolution angiography of the organ matrix. The whole rat kidney is decellularized using a new multistep perfusion protocol with the combined use of Triton X-100 and DNase. The decellularized kidney matrix is then cryopreserved after the pretreatment with different cryoprotectant solutions. The reconstructed tomographic images from Micro-CT confirm various structural alterations in the vasculature of the whole decellularized kidney matrix with/without frozen storage. The freezing damage to the vascular architectures can be reduced by perfusing cryoprotectant solutions into the whole kidney matrix. Ice-free cryopreservation with the vitrification solution VS83 can successfully preserve the integrity of the whole kidney matrix's vasculature after frozen storage., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Two novel heterowheel [4]pseudorotaxanes consisting of cucurbit[7]uril (Q[7]) and symmetrical-tetramethyl-cucurbit[6]uril (TMeQ[6]) were constructed via the multirecognition mechanism, in which Q[7] can rotate freely around the horizontal axis, while TMeQ[6] cannot. In the construction process, due to strong repulsive forces between carbonyl portals of two neighboring wheels, the dethreading and movement of the wheels along the axle was observed. The dissociation of the [4]pseudorotaxanes was also discussed.

Objective: To investigate and analyze the relationship between intraoperative graft flow measurements and the early mid-term outcomes after off-pump coronary artery bypass grafting (OPCAB)., Methods: Patients who underwent isolated OPCAB in the Department of Cardiac Surgery of Peking University People's Hospital from January 2013 to June 2016 were included. Perioperative characteristics, graft flow measurements and postoperative follow-up outcomes were retrospectively collected. Comparison was made between flow measurements of grafts and the early mid-term outcomes. Flow measurements of grafts included the mean flow (MF) and the pulsatility index (PI). The early outcomes included peri-operative myocardial infarction (PMI), use of an intra-aortic balloon pump (IABP), reoperation for all causes, new-onset atrial fibrillation and in-hospital or 30-day mortality., Results: A total of 463 patients were included in the study. Mean age was (62.80±8.36) years, and 24.8% were females. The total number of grafts was 1 435, which averaged 3.10 grafts per patient. The MF and PI were separately (32.34±14.45) mL/min and 2.87±0.92. Of all the patients, 23(5%) had PMI, and 11 used IABP. Observed in-hospital or 30-day mortality was 0.86% (4 patients). Compared with non-PMI group, the MF was lower and the PI was higher in the PMI group (P<0.05). However, the differences of other early outcomes had no statistical significance between the PMI group and the non-PMI group. The lower MF (Wald=5.684, P=0.017, 95%CI: 0.894-0.989) and the higher PI (Wald=9.040, P=0.003, 95%CI: 1.252-2.903) were risk factors of PMI in multivariable Logistic regression modeling. The longest follow-up time was 37 months, and 7 patients died. The differences of graft flow measurements between the surviving group and the nonsurvivors had no statistical significance, but overall mid-term survival was lower in patients with poor left internal mammary artery (LIMA) to left anterior descending artery (LAD) graft flow (MF<10 mL/min; OR=9.6, P<0.05)., Conclusion: Intraoperative graft flow parameters during OPCAB can predict the early mid-term outcomes. The lower MF and the higher PI should increase the rate of PMI. A lower flow of LIMA to LAD graft (<10 mL/min) should increase the rate of midterm mortality, but further research will be needed to confirm and explore the findings.

Background: Glycerol, sucrose and trehalose are used as protectants for membrane, protein, cell and tissue preservation. The undercooled state (glassy or rubbery) of their solutions may also offer protection for protein, cells and tissues against radiation damage upon sterilization., Objective: The study aimed to examine the protective effects of glycerol, sucrose and trehalose on cryopreserved acellular human dermis against gamma irradiation damage., Materials and Methods: Acellular human dermis was cryopreserved at -80°C in glycerol, sucrose and trehalose solutions or their combinations with a base citrate-phosphate buffer (pH 6.0). Cryopreserved acellular dermis was then subjected to 13 kGy gamma irradiation at -78.5°C, and radiation damage was assessed by histological evaluation., Results: Freeze and thaw alone do not alter the structure of acellular dermis, but gamma irradiation at -78.5°C results in significant structural changes in acellular dermis, including the formation of large holes, the damage of collagen fibers and the loss of overall dermis tissue histology. The incorporation of glycerol, sucrose and trehalose into cryopreservation solutions reduces gamma irradiation-induced tissue structural damage considerably. When used alone, trehalose (0.5 M) provided better protection against gamma irradiation damage than did sucrose (0.5 M) and glycerol (1.0 M). When used in combination, the glycerol and trehalose combination provides the best tissue protection. Significant donor-to-donor variation exists in tissue damage after gamma irradiation. For donor dermis that is less sensitive to gamma irradiation damage, glycerol, sucrose or trehalose alone is able to provide good protection. However, for more sensitive donor dermis, only the glycerol and trehalose combination is able to provide sufficient tissue protection., Conclusion: Glycerol, sucrose and trehalose protects cryopreserved acellular human dermis against gamma irradiation damage. Cryopreservation solutions can be optimized to permit tissues for gamma sterilization to increase the safety human tissue implants.

Objective: To evaluate the clinical significance and molecular mechanism of bladder cancer-associated transcript 1 (BLACAT1) in non-small-cell lung cancer (NSCLC)., Patients and Methods: Overall, 156 NSCLC cancer patients were recruited and divided into high and low BLACAT1 level group by the median value of BLACAT1 expression. The associations of BLACAT1 expression with the clinicopathological features and prognosis were evaluated. A series of in vitro assays were performed to explore the role of BLACAT1 on NSCLC progression and metastasis., Results: Patients with high BLACAT1 expression had shorter overall survival and progression-free survival than those with low BLACAT1 expression. Multivariate analyses showed that BLACAT1 was an independent prognostic factor of survival in NSCLC patients. In vitro assays showed that the downregulation of BLACAT1 significantly suppressed cell progression, migration, and invasion. The epithelial-mesenchymal transition was also inhibited when BLACAT1 was silenced, indicated by an increase in E-cadherin expression and a decrease in vimentin expression by mediating Wnt/β-catenin signaling pathway., Conclusions: BLACAT1 should be a potential prognostic biomarker and therapeutic target for NSCLC.

Alpha-tricalcium phosphate (α-TCP) based porous scaffolds have superior osteoconduction and osteoinduction in bone tissue engineering, furthermore, these 3D porous scaffolds can be used as efficient drug delivery carriers. In the concept of tissue engineering, the "drugs" could be defined as drug molecules or biomacromolecules, even cells. These "drugs" have endowed the scaffolds which were laden improved abilities compared with the blank scaffolds. In this study, we anchored osteogenic bone morphogenetic protein-2 (BMP-2) derived peptides to α-TCP 3D porous scaffolds by linking the E7 domain to the target peptides, constructed the modified active peptides (E7BMP-2 peptides) delivery system, which finally achieved the modified peptides sustaining release and enhanced rat bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in vitro. The α-TCP 3D porous scaffolds had micropores and interconnected micropores which expanded surface area of the scaffolds. The release test testified the constructed the delivery system had realized long-term release in which the peptides dosage could be detected by the BCA protein assay kit after 10 days compared with BMP-2 proteins which absorbed on the same α-TCP 3D porous scaffolds. The constructed E7BMP-2 peptides delivery system supported rat BMSCs osteogenic differentiation in the form of improving the genes expression levels of Runx2, ALP and OCN. Based on electrostatic interactions, E7 domain fastened combination between the active BMP-2 derived peptides and the α-TCP 3D porous scaffolds, the sustaining E7BMP-2 peptides release promoted the BMSCs osteogenesis as BMP-2 proteins did, which endowed α-TCP 3D porous scaffolds enhanced osteoinductive abilities in vitro., (Copyright © 2018. Published by Elsevier B.V.)

To investigate the particulate matter emission characteristics of various emitting sources of the coking process of iron and steel plants, an automatic dust (smoke) tester and an eight-staged Anderson sampler were employed to conduct onsite sampling of particulate matter emissions from the coking process, including coal loading and coke pushing, coke dry quenching exhaust and coke screening and transferring in a steel plant, based on the measurement of particulate matter in the exhaust of fixed sources and sampling of gaseous pollutants. The morphology, particle size distribution, and chemical composition of the particulate matter from different sources were investigated. The results show that the single particles can be divided into five categories:iron-rich, silicon-rich, calcium-rich, carbon, and smoke polymer. They mainly appear in four forms:polygon block, irregular lamellae, lumps, and floc. The particle size of the coal loading and coke pushing unit mainly is 3.3-4.7 μm, while it is 3.3-4.7 μm and 5.8-9.0 μm for the dry quenching exhaust and 4.7-5.8 μm for the coke screening and transferring unit. The main chemical components of particulate matter in the coking process are C, SiO 2 , Al 2 O 3 , S, CaO, and TFe, with contents of 76.30%-81.30%, 5.36%-5.91%, 3.96%-4.26%, 1.15%-1.34%, 0.52%-1.59%, and 0.81%-1.34%, respectively.

Colorectal carcinoma is currently the third most frequent cancer worldwide. Conventional open surgery was replaced by laparoscopic anterior resection with total mesorectal excision for the treatment of sigmoid and rectal carcinomas; however, it needed an incision to harvest the specimen, which contributed to complications. In 2013, trans-anal natural orifice specimen extraction laparoscopic anterior resection (Ta-NOSE-LAR) to treat sigmoid and rectal carcinoma was performed in our hospital for the first time. The aim of this study was to investigate the outcomes of Ta-NOSE-LAR in sigmoid and rectal carcinoma.Seventy-three patients diagnosed with sigmoid and rectal carcinoma were enrolled between September 2013 and June 2016. Thirty-five patients underwent Ta-NOSE-LAR, whereas the others underwent traditional laparoscopic anterior resection (LAR). We compared the operative data, postoperative complications, pathological evaluation results, and incision-related complications between the 2 groups.Our result showed that the operative time, specimen length, tumor size, amount of total lymph nodes, and lymph node metastasis between the 2 groups were not statistically different. Further, without abdominal scaring for harvesting the specimen, the operative blood loss (49.29 ± 14.63 vs 69.29 ± 13.54 mL, P < .001) and post-operation hospital stay (5.77 ± 0.94 vs 6.76 ± 0.75 days, P < .001) of the Ta-NOSE-LAR group were less than those of the LAR group. Besides, the follow-up data showed that 2 patients were lost to follow-up, and 1 patient had liver metastasis 2 years after surgery in the LAR group, whereas the others showed no regional recurrence, distant metastases, or critical complications.Ta-NOSE-LAR is a valuable and alternative surgical method to treat sigmoid and rectal carcinoma, with the advantages of being a scarless procedure and having a lower post-operation hospital stay duration.

A novel heterometallic diPd II -diCu II grid-chain, {[(bpy) 4 Pd 4 Cu 2 L 4 ](NO 3 ) 4 } n (2; bpy=2,2'-bipyridine), was synthesized through a programmable self-assembly approach from the molecular corners [(bpy) 2 Pd 2 (HL)(L)](NO 3 ) (1) as linkers with Cu II nitrate by using the bifunctional H 2 L ligand featuring primary (pyrazole) and secondary (benzoic acid) groups. Structural analysis revealed that 1D structure 2 consists of one [Cu 2 (O 2 CPh) 4 ] n unit as a bridge and two [(bpy) 2 Pd 2 L 2 ] n corners. Additionally, the catalytic effect of the heterometallic synergy on the Suzuki coupling reaction by using 2 was further explored., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) is a potential therapeutic target in acute coronary syndromes. Although recent evidence does not support the routine use of manual thrombus aspiration (TA) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), the use of TA is associated with a significant improvement in myocardial reperfusion, especially in patients with high thrombus burden (HTB). We hypothesized that TA would reduce the serum Lp-PLA 2 levels in STEMI patients undergoing PPCI with HTB., Methods and Results: Our study cohort included 320 consecutive STEMI patients undergoing PPCI with HTB who were randomly assigned to receive either TA before PPCI (TA group, n = 160) or PPCI alone (standard PPCI group, n = 160). The baseline characteristics of study participants were well-matched. After 30 ± 2 days, serum Lp-PLA 2 levels decreased by 53.9% in the TA group (152.9 ± 58.1 ng/mL) and decreased by 31.2% in the standard PPCI group (84.2 ± 86.6 ng/mL, p < 0.001). The TA group had a significantly lower prevalence of balloon predilatation, number of stents used, total stent length and corrected thrombolysis in myocardial infarction frame count, and a higher percentage of myocardial blush grade ≥ 2 compared with the standard PPCI group (all p < 0.001). No significant difference between the groups was observed in 30 ± 2 days for major adverse cardiovascular and cerebrovascular events (p = 0.702)., Conclusions: After 30 ± 2 days of treatment, TA may significantly reduce serum levels of Lp-PLA 2 in STEMI patients undergoing PPCI with HTB.

A kind of gold nanoparticles modified with metal crown ether porphyrin (GNPs-CP) was synthesized and characterized. The surface of the resulting gold particles was partially covered by metal crown ether porphyrin molecules through strong covalent Au-S bond. Based on the coupling effect of metal porphyrin and crown ether, the resulting composite gold nanoparticles can serve as a kind of ion probe. Raman and UV-Vis spectra were utilized to evaluate the ion recognition of the system, both of which changed dramatically when meeting metal ion corresponding to ligand of crown ether. Compared with UV-Vis spectra, Raman spectra of the composites are more sensitive and the limit of detection (LOD) can reach 1 × 10-8 g/mL. The study provides a candidate with higher sensitivity to replace current UV-Vis spectrum based evaluation tool for ion recognition.

Genipin, a natural compound derived from the fruit of Gardenia jasminoides , possesses numerous biological properties. The aim of the present study was to investigate the anticancer effects of genipin in human bladder cancer. T24 and 5637 bladder cancer cells were treated with different concentrations of genipin (0-200 µM) and tested for cell viability, colony formation, cell cycle progression and apoptosis. A xenograft model of bladder cancer was established to determine the anticancer effect of genipin in vivo . The involvement of the phosphoinositide-3 kinase (PI3K)/Akt pathway in the action of genipin was examined. Genipin treatment significantly inhibited the viability and clonogenic growth of bladder cancer cells and inhibited the growth of T24 xenograft tumors, compared with vehicle controls (P<0.05). Genipin-treated cells exhibited a cell cycle arrest at the G0/G1-phase, which was accompanied by a deregulation of numerous cell cycle regulators. Genipin-treated cells demonstrated a significant increase in the percentage of apoptotic cells, loss of mitochondrial membrane potential, Bax translocation to the mitochondria and the release of cytochrome c to the cytosol. Additionally, genipin treatment significantly (P<0.05) reduced the phosphorylation levels of PI3K and Akt in bladder cancer cells. Importantly, genipin-mediated anticancer effects were reversed by the overexpression of constitutively active Akt. In conclusion, to the best of our knowledge, the present study demonstrates for the first time the growth inhibitory effects of genipin in bladder cancer cells, and indicates its potential as a natural anticancer agent for bladder cancer.

Background: Recently, increasing reports showed that the risk of fracture may be correlated with type 2 diabetes mellitus (T2DM). However, their results still remained controversial. Thus we performed a meta-analysis including 11 studies to estimate the risk factor of limb fracture in type 2 diabetes mellitus., Materials and Methods: Databases including PubMed, Embase, Cochrane Library and Web of Science were searched to September, 2017. Risk Ratio (RR) with its 95% confidence intervals (CI) was used to evaluate the association between risk of limb fracture and type 2 diabetes mellitus. Two reviewers assessed the quality of all the included studies and extracted data for analysis independently., Results: A total of 11 studies including 663,923 participants were included in this meta-analysis. Our analysis results showed that patients with type 2 diabetes mellitus had a significant association with risk of limb fracture (RR 1.18; 95% CI 1.02-1.35), including leg or ankle fracture (RR 1.80; 95% CI 1.13-2.87). Subgroup analysis showed individuals with type 2 diabetes had almost two-fold excessive risk of leg/ankle fracture in women and the pooled RR of leg/ankle fracture was 2.03 (95% CI 1.36-3.05; P = 0.0006)., Conclusions: The results of the present meta-analysis showed that individuals with type 2 diabetes mellitus had higher risk of limb fractures, and this relationship is more pronounced in leg or ankle fracture., Competing Interests: CONFLICTS OF INTEREST The author declared no conflicts of interests.

Background: Chemoresistance is a major obstacle that limits the benefits of 5-Fluorouracil (5-Fu)-based chemotherapy for colon cancer patients. Autophagy is an important cellular mechanism underlying chemoresistance. Recent research advances have given new insights into the use of natural bioactive compounds to overcome chemoresistance in colon cancer chemotherapy. As one of the multitargeted and safer phytomedicines, curcumin has been reported to work as cancer-specific chemosensitizer, presumably via induction of autophagic signaling pathways. The precise therapeutic effect of curcumin on autophagy in determining tumorous cells' fate, however, remains unclear. This study was conducted to investigate the differential modulations of the treatments either with 5-Fu alone or 5-Fu combined with curcumin on cellular autophagic responses and viabilities in the human colon cancer cells HCT116 and HT29, and explore molecular signaling transductions underlying the curcumin-mediated autophagic changes and potentiation of 5-Fu's cytotoxicity in vitro and in vivo., Methods: Cell proliferation assay and morphology observation were used to identify the cytotoxicity of different combinations of curcumin and 5-Fu in HCT116 and HT29 cells. Cell immunofluorescence assay, Flow cytometry and Western blot were employed to detect changes of autophagy and the autophagy-related signaling pathways in the colon cancer cells and/or xenograft mice., Results: Curcumin could significantly augment the cytotoxicity of 5-Fu to the tumorous cells, and the pre-treatment with curcumin followed by 5-Fu (pre-Cur) proved to be the most effective one compared to other two combinations. The chemosensitizing role of curcumin might attribute to the autophagy turnover from being activated in 5-Fu mono-treatment to being inhibited in the pre-Cur treatment as indicated by the changes in expression of beclin-1, p62 and LC3II/LC3I and the intensity of Cyto-ID Green staining. The autophagic alterations appeared to be contributed by down-regulation of not only the phospho-Akt and phospho-mTOR expressions but the phospho-AMPK and phospho-ULK1 levels as well. The cellular activation of AMPK by addition of A-769662 to the pre-Cur combination resulted in reversed changes in expressions of the autophagy protein markers and apoptotic status compared to those of the pre-Cur combination treatment. The findings were validated in the xenograft mice, in which the tumor growth was significantly suppressed in the mice with 25-day combination treatment, and meanwhile expressions of the autophagy markers, P-AMPK and P-ULK1 were all reversely altered in line with those observed in HCT116 cells., Conclusion: Pre-treatment with curcumin followed by 5-Fu may mediate autophagy turnover both in vitro and in vivo via AMPK/ULK1-dependent autophagy inhibition and AKT modulation, which may account for the increased susceptibility of the colon cancer cells/xenograft to the cytotoxicity of 5-Fu.

In this work, we designed and synthesized a special axle guest hexyldimethyl(ferrocenylmethyl)ammonium ( 1 + ) bromide. The binding interactions of 1 + and its oxidized form 1 2+ with cucurbit[7]uril (Q[7]) and cyclohexanocucurbit[6]uril (Cy6Q[6]) were investigated by 1 H NMR, cyclic voltammogram, and isothermal titration calorimetry techniques. Our data indicate that both hosts Cy6Q[6] and Q[7] can form stable [2]pseudorotaxanes with 1 + in their different redox states. Most importantly, the combination and dissociation of the hosts with the guest as well as the binding location can be controlled by electrochemical means, which develops a special molecular switch and selector., Competing Interests: The authors declare no competing financial interest.