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Aims This study aimed to separate the effects of chemical and microbial factors on the fermentation quality and bacterial community of ensiled Pennisetum giganteum. Methods and Results Fresh P. giganteum of two vegetative stages (stage I, GI; stage II, GII) was treated as follows: GI epiphytic microbiota + γ-ray presterilized GI (MICI), GII epiphytic microbiota + γ-ray presterilized GI (MIICI), GI epiphytic microbiota + γ-ray presterilized GII (MICII), and GII epiphytic microbiota + γ-ray presterilized GII (MIICII). Triplicates per treatment were sampled after 30 days of ensiling for chemical and microbial analyses and high-throughput sequencing. Silages made from CII (MICII and MIICII) had higher lactic acid concentration and the ratio of lactic to acetic acid, and lower pH and ammonia nitrogen concentration than silages produced by CI (MICI and MIICI). Species differential analyses showed that the changes of chemical composition rather than epiphytic microbiota significantly affected the relative abundance of Lactobacillus, Pediococcus and Pantoea in P. giganteum silages. Conclusion These above results manifested that chemical composition was the main factor influencing the fermentation quality and bacterial community of P. giganteum silage in this study. Significance and Impact of the Study The obtained results may, therefore, be the first record to provide an in-depth understanding of the relative contributions of chemical and microbial parameters on fermentation quality and bacterial community, which is of great importance for modulating silage fermentation and improving silage quality.

Targeting the potential application of morphological carbon in electrode materials, a space-sacrificed pyrolysis strategy was applied for the preparation of boron-doped carbon spheres (B-CSs), using commercial triphenyl borate (TPB) as carbon and boron co-source. The unique structure of TPB play an important role in the sacrificed space, and has notable effect on the surface area of B-CSs. The as prepared B-CSs possess a high surface area and boron content with uniform boron atoms distribution and high surface polarity, which contributes to the improvement of pseudo-capacitance. The sizes, specific surface areas, and boron contents of B-CSs can be easily regulated by varying the experimental parameters. The optimal sample has a boron content of 1.38 at%, surface area of 560 m2 g−1 and specific capacitance of 235F g−1. We can believe that this work would provide a flexible and extensible preparation technique of B-CSs for electrochemical applications.

Aims: Repurposing of drugs has been hypothesized as a means of identifying novel treatment methods for certain diseases. Background: Glioblastoma (GB) is an aggressive type of human cancer; the most effective treatment for glioblastoma is chemotherapy, whereas, when repurposing drugs, a lot of time and money can be saved. Objective: Repurposing of the existing drug may be used to discover candidate drugs for individualized treatments of GB. Method: We used the bioinformatics method to obtain the candidate drugs. In addition, the drugs were verified by MTT assay, Transwell® assays, TUNEL staining, and in vivo tumor formation experiments, as well as statistical analysis. Result: We obtained 4 candidate drugs suitable for the treatment of glioma, camptothecin, doxorubicin, daunorubicin and mitoxantrone, by the expression spectrum data IPAS algorithm analysis and drug-pathway connectivity analysis. These validation experiments showed that camptothecin was more effective in treating the GB, such as MTT assay, Transwell® assays, TUNEL staining, and in vivo tumor formation. Conclusion: With regard to personalized treatment, this present study may be used to guide the research of new drugs via verification experiments and tumor formation. The present study also provides a guide to systematic, individualized drug discovery for complex diseases and may contribute to the future application of individualized treatments.

The acetonitrile solvate of a Schiff base molecule (HL) with acetonitrile (HL·2CH3CN) and its Cd(II) complex (Cd(HL)2Cl2, 1) were designed and synthesized. The different conformation of HL in HL·2CH3CN is adjusted by the hydrogen bonding O-H···O between HL molecules, together with N-H···N between HL molecules and acetonitrile molecules. While the conformation of HL in complex 1 is adjusted by coordination interactions between Zn ions and atoms O and N, together with hydrogen bonding N-H···Cl. The presence of the triphenylamine group makes HL·2CH3CN and complex 1 loosely packed. Upon grinding, HL·2CH3CN and complex 1 both showed high-contrast mechanochromic luminescence (MCL) change from blue to green and cyan to yellow, respectively. These changes can be eliminated by fumigation with organic vapor. The results of powder X-ray diffraction (PXRD) show that their MCL is due to the phase transformation from crystalline to amorphous state. In addition, HL·2CH3CN and complex 1 also exhibited high-contrast acidochromism upon exposure to HCl and NH3 vapor. X-ray photoelectron spectroscopy (XPS) and PXRD studies show that the protonation of the -NH- group together with a phase transformation from crystalline to amorphous state is attributed to the fluorescence switching. For HL·2CH3CN, the protonation process was accompanied by the departure of acetonitrile molecules. The emission of HL was restored to the amorphous state rather than the original crystalline state emission after further exposure to NH3 vapor, while 1-HCl could restore to the original crystalline state emission. In addition, HL·2CH3CN and complex 1 have been successfully used to produce writable and acid-responsive test papers.

Background: Staphylococcus aureus biofilms were linked to negative postsurgical outcomes of chronic rhinosinusitis (CRS). This study aims to develop a targeted nanoparticle and characterize its bactericidal effects. Methods: The authors prepared ISMN-loaded poly-lactide-co-glycolide acid (PLGA) and polyethylene glycol (PEG) nanoparticles conjugated with anti- S. aureus α-toxin (AA; ISMN-PLGA-PEG-AA), and determined its bactericidal and toxic effects. The antibiofilm propriety of ISMN-PLGA-PEG-AA was further investigated in a sheep CRS model. Results: ISMN-PLGA-PEG-AA had no toxic effect, while ISMN, ISMN-PLGA-PEG and ISMN-PLGA-PEG-AA had significantly anti- S. aureus effects. The blood concentrations and mRNA levels in sinus tissues of IL-4, IL-8 and IFN-γ in the sheep CRS model were significantly low. Conclusion: ISMN-PLGA-PEG-AA can effectively inhibit S. aureus biofilm, and is a promising drug for CRS treatment.

A triphenylamine (TPA)-based 2H-quinazoline Zn(II) complex (Q-TPA-Zn) exhibiting dual fluorescence and phosphorescence emission in the solid state was designed and prepared. It possesses mechanochromic luminescence and thermochromic luminescence properties. In the solid state, the white afterglow luminescence could be observed at 77 K (CIExy: 0.27, 0.33) while cyan luminescence could be observed at 297 K. After thermolysis at 300 °C, Q-TPA-Zn could be transformed into Schiff base complex S-TPA-Zn with white fluorescence in the powder state (CIExy: 0.32, 0.38), in methanol (CIExy: 0.32, 0.39), and in dimethylformamide (CIExy: 0.26, 0.32) at room temperature. This arises from dual emission of normal* emission and tautomeric* emission induced by excited-state intramolecular proton transfer (ESIPT) from the benzimidazole NH group to the Schiff base N atom. Q-TPA-Zn could also be transformed into its isomeric form, S-TPA-Zn, through photochemical ring-opening reaction upon irradiation under 365 nm in the solution, exhibiting high-contrast photochromic luminescence. Interestingly, S-TPA-Zn could further be transformed into its zwitterionic isomer after continuous irradiation. The same ring-opening reaction could also take place for the orgainc compound Q-TPA via heating or 365 nm irradiation. The ring-opening reaction mechanism and ESIPT emission were interpreted via theoretical calculation.

The Schottky barrier at the interface between the semiconductor phase and the metal phase has excellent rectification effect which can greatly facilitate the formation of the electron accumulation region. The interface electronic modulation can promote the formation of electron depletion layer in the gas sensing process, which is a powerful strategy to improve the sensing performance. In this work, ZnO–TiC composites were successfully prepared. XRD, TEM, BET and XPS characterizations of the ZnO–TiC composites were proformed to investigate the compositions and structures. The as-synthesized samples were applied to fabricate gas sensors to investigate their gas sensing performance. Compared to pure ZnO and TiC, the composites achieved high sensitivity (232 for 100 ppm aniline) and linear detection (R2 = 0.986) of aniline. The improvement of sensor performance is mainly attributed to the electronic modulation of Schottky barrier at the interface between ZnO and TiC. Our results indicate that the construction of ZnO-TiC Schottky barrier is a promising strategy for enhancing the performance of gas sensors.

Vascular calcification is highly prevalent in chronic kidney disease (CKD), and is characterized by transdifferentiation from contractile vascular smooth muscle cells (VSMCs) into an osteogenic phenotype. However, no effective and therapeutic option to prevent vascular calcification is yet available. Dihydromyricetin (DMY), a bioactive flavonoid isolated from Ampelopsis grossedentata, has been found to inhibit VSMCs proliferation and the injury-induced neointimal formation. However, whether DMY has an effect on osteogenic differentiation of VSMCs and vascular calcification is still unclear. In the present study, we sought to investigate the effect of DMY on vascular calcification in CKD and the underlying mechanism. DMY treatment significantly attenuated calcium/phosphate-induced calcification of rat and human VSMCs in a dose-dependent manner, as shown by Alizarin Red S staining and calcium content assay, associated with down-regulation of osteogenic markers including type I collagen (COL I), Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2) and osteocalcin (OCN). These results were further confirmed in aortic rings ex vivo. Moreover, DMY ameliorated vascular calcification in rats with CKD. Additionally, we found that AKT signaling was activated during vascular calcification, whereas significantly inhibited by DMY administration. DMY treatment significantly reversed AKT activator-induced vascular calcification. Furthermore, inhibition of AKT signaling efficiently attenuated calcification, which was similar to that after treatment with DMY alone, and DMY had a better inhibitory effect on calcification as compared with AKT inhibitor. The present study demonstrated that DMY has a potent inhibitory role in vascular calcification partially by inhibiting AKT activation, suggesting that DMY may act as a promising therapeutic candidate for patients suffering from vascular calcification.

Prion disease (PrD) and Parkinson's disease (PD) are neurodegenerative diseases characterized by aggregation of misfolded proteins in brain tissues, including protease-resistant prion protein (PrPSc) in PrD and α-synuclein in PD. In recent years, overlap of these two proteins has attracted increased attention, and cross-seeding of prion proteins by aggregated α-synuclein has been proposed. However, the changes in α-synuclein after prion infection are still unclear. In this study, we showed that α-synuclein expression was significantly decreased in the brains of prion-infected rodent models, in the SMB-S15 cell line, which exhibits persistent prion replication, and in the brains of humans with PrDs. Meanwhile, α-synuclein phosphorylated at serine 129(p(S129)-α-synuclein) was significantly increased in the brains of scrapie-infected mice and prion-infected SMB-S15 cells. The increased p(S129)-α-synuclein colocalized with GFAP- and NeuN-positive cells in the brains of scrapie-infected mice. p(S129)-α-synuclein was also observed in the cytoplasm of SMB-S15 and HEK-293 cells transiently expressing an abnormal form of prion protein (Cyto-PrP). Molecular interactions between PrP and α-synuclein were detected in recombinant proteins, normal and prion-infected brain tissues, and cultured cells. The increased p(S129)-α-synuclein colocalized with PrP signals from prion-infected SMB-S15 and HEK-293 cells expressing Cyto-PrP. Moreover, increased morphological colocalization of p(S129)-α-synuclein with mitochondrial markers was also detected in the two cell types. Our results indicate that prion replication and accumulation in cells and brains induce hyperphosphorylation of α-synuclein, particularly at S129, which may aggravate mitochondrial damage and facilitate α-synuclein aggregation in the central nervous system tissues from PrDs.

AIMS To investigate the effects of epiphytic microbiota from napiergrass and Sudan grass on ensiling characteristics and microbial community of oat silage. METHODS AND RESULTS By γ-ray irradiation sterilization and microbiota transplantation technology, the sterilized oat was inoculated as follows: (a) aseptic water (STOT), (b) epiphytic bacteria on oat (OTOT), (c) epiphytic bacteria on napiergrass (OTNP) and (d) epiphytic bacteria on Sudan grass (OTSD). STOT remained in the unfermented state based on similar chemical components with fresh oat. Compared with OTOT and OTSD, higher lactic acid content and ratio of lactic acid to acetic acid, and lower pH, acetic acid and ammonia nitrogen contents were observed in OTNP after 60 days of ensiling. At the late stage, Lactobacillus was the most predominant in each group. Lactococcus was eventually replaced by Lactobacillus in OTSD, whereas Lactococcus was found throughout the whole ensiling process in OTNP. Higher abundance of Weissella was observed in OTSD at the early and late stages. The result of co-occurrence network analysis proved that Lactococcus was pivotal in determining the silage fermentation pattern during ensiling. According to the 16S rRNA gene-predicted functional profiles, the inoculation of epiphytic microbiota from oat enhanced the metabolism of amino acids, whereas the inoculation of epiphytic microbiota from napiergrass and Sudan grass accelerated the carbohydrate metabolism. CONCLUSIONS The epiphytic microbiota on napiergrass promoted a homo-fermentative process, whereas the epiphytic microbiota on oat and Sudan grass facilitated a hetero-fermentative pattern in oat silage, which was closely related to the abundance and metabolism of Lactococcus, Weissella and Lactobacillus. SIGNIFICANCE AND IMPACT OF THE STUDY The exogenous microorganisms that promote the carbohydrate metabolism and inhibit the metabolism of amino acids could be a good potential source to improve the silage quality of temperate grass.

Astaxanthin (AST) has a variety of biochemical effects, including anti-inflammatory, antioxidative, and antihypertensive functions. The aim of the present study was to determine whether AST ameliorates blood pressure in salt-induced prehypertensive rats by ROS/MAPK/NF-κB pathways in hypothalamic paraventricular nucleus. To explore the central effects of AST on the development of blood pressure, prehypertensive rats were induced by a high-salt diet (HS, 8% NaCl) and its control groups were treated with normal-salt diet (NS, 0.3% NaCl). The Dahl salt-sensitive (S) rats with HS diet for 6 weeks received AST or vehicle by gastric perfusion for 6 weeks. Compared to those with NS diet, rats with HS diet exhibited increased mean arterial pressure (MAP) and heart rate (HR). These increases were associated with higher plasma level of norepinephrine (NE), interleukin 1β (IL-1β), and interleukin 6 (IL-6); elevated PVN level of reactive oxygen species (ROS), NOX2, and NOX4, that of IL-1β, IL-6, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), phosphorylation extracellular-signal-regulated kinase (p-ERK1/2), phosphorylation Jun N-terminal kinases (p-JNK), nuclear factor-kappa B (NF-κB) activity; and lower levels of IL-10, superoxide dismutase (SOD), and catalase (CAT) in the PVN. In addition, our data demonstrated that chronic AST treatment ameliorated these changes in the HS but not NS diet rats. These data suggested that AST could alleviate prehypertensive response in HS-induced prehypertension through ROS/MAPK/NF-κB pathways in the PVN.

Introduction Berberine (BBR), as one of the outstanding representatives of isoquinoline alkaloids, has been used as an antibacterial drug for a long time in China since ancient times. Currently, a large number of studies have been reported that berberine has a wide spectrum of pharmacological activities, such as anti-tumor, anti-inflammatory, hypoglycemic, hypolipidemic, anti-obesity, and the like. Areas covered This review systematically discussed important patents on berberine and berberine derivatives in terms of pharmacological activity between 2016 and 2020. These patents were mainly searched through the European Patent Office database and Web of Science. These berberine patents (~41) cover a wide range of applications, mainly including antitumor, anti-inflammatory, antibacterial, anti-metabolic disorder, and other newly reported pharmacological activities. Expert opinion Berberine is an important lead compound with great potential for optimization in drug development. However, there is a lack of research related to the biomolecular targets of BBR, which directly restricts the development of berberine in the pharmaceutical field. The problems involved with poor bioavailability and cytotoxicity are also worth considering in the development of berberine-based drugs. Accordingly, the increasing number of patents involving biomolecular targets in BBR's patent applications will be published as its related pharmacological mechanisms are further deciphered.

Aberrant activation of NLRP3 inflammasome in colonic macrophages strongly associates with the occurrence and progression of ulcerative colitis. Although targeting NLRP3 inflammasome has been considered to be a potential therapy, the underlying mechanism through which pathway the intestinal inflammation is modulated remains controversial. By focusing on the flavonoid lonicerin, one of the most abundant constituents existed in a long historical anti-inflammatory and anti-infectious herb Lonicera japonica Thunb., here we report its therapeutic effect on intestinal inflammation by binding directly to enhancer of zeste homolog 2 (EZH2) histone methyltransferase. EZH2-mediated modification of H3K27me3 promotes the expression of autophagy-related protein 5, which in turn leads to enhanced autophagy and accelerates autolysosome-mediated NLRP3 degradation. Mutations of EZH2 residues (His129 and Arg685) indicated by the dynamic simulation study have found to greatly diminish the protective effect of lonicerin. More importantly, in vivo studies verify that lonicerin dose-dependently disrupts the NLRP3–ASC–pro-caspase-1 complex assembly and alleviates colitis, which is compromised by administration of EZH2 overexpression plasmid. Thus, these findings together put forth the stage for further considering lonicerin as an anti-inflammatory epigenetic agent and suggesting EZH2/ATG5/NLRP3 axis may serve as a novel strategy to prevent ulcerative colitis as well as other inflammatory diseases., Graphical abstract Lonicerin can be considered as an anti-inflammatory epigenetic agent and EZH2/ATG5/NLRP3 axis may serve as a novel strategy to prevent ulcerative colitis as well as other inflammatory diseases.Image 1

It is necessary to develop stable and fast multistimuli responsive materials due to the growing demand in our daily life. In this work, a new viologen-based Cd-complex (1) exhibits multiple thermochromic and photochromic behaviors through 10 states with 7 colors. For example, it responds to both Cu Kα/Mo Kα X-ray sources and UV dual light quickly with a color change from colorless to dark blue (1X) (Cu Kα/Mo Kα X-ray sources) and cyan (1-UV) (UV light), respectively. Interestingly, it exhibits a three-step coloration phenomenon when heated, which is unprecedented in viologen compounds. Crystal 1 undergoes a color change to pink, blue, and brown under 130, 180, and 240 °C, respectively. In addition, upon fumigation, both 1P and 1Q undergo a decoloration process to colorless (1K) and yellow (1T), respectively. Four more states (1P, 1K, 1T, and 1O) obtained via dehydration-hydration treatment are all photochromic. More importantly, via single-crystal-single-crystal transformation (SC-SC), the photochromic and thermochromic behaviors of 1 were investigated from the molecular level, which is also rather rare for thermochromic species. The detailed electron donor and the pathways for electron transfer were clearly given according to the results of crystal structure. The colorful states upon external stimuli may be attributed to the multiple pathways for electron transfer.

Bone cancer pain (BCP) is a clinical pathology that urgently needs to be solved, but research on the mechanism of BCP has so far achieved limited success. Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) has been shown to be involved in pain, but its involvement in BCP and the specific mechanism have yet to be examined. This study aimed to test the hypothesis that BCP induces the transfer of Nrf2 from the cytoplasm to the nucleus and further promotes nuclear transcription to activate heme oxygenase-1 (HO-1) and inhibit the activation of nuclear factor-kappa B (NF-κB) signalling, ultimately regulating the neuroinflammatory response. Von-Frey was used for behavioural analysis in rats with BCP, whereas western blotting, real-time quantitative PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect molecular expression changes, and immunofluorescence was used to detect cellular localization. We demonstrated that BCP induced increased Nrf2 nuclear protein expression with decreased cytoplasmic protein expression in the spinal cord. Further increases in Nrf2 nuclear protein expression can alleviate hyperalgesia and activate HO-1 to inhibit the expression of NF-κB nuclear protein and inflammatory factors. Strikingly, intrathecal administration of the corresponding siRNA reversed the above effects. In addition, the results of double immune labelling revealed that Nrf2 and NF-κB were coexpressed in spinal cord neurons of rats with BCP. In summary, these findings suggest that the entry of Nrf2 into the nucleus promotes the expression of HO-1, inhibiting activation of the NF-κB signalling pathway, reducing neuroinflammation and ultimately exerting an anti-nociceptive effect.

Introduction Alcohol consumption has been steadily increasing in East Asia, however, there is comparatively little regional data of alcohol-related harms. This study examines the alcohol-related harms prevalence and risk factors in Hong Kong, a high population density city with limited alcohol regulation. Methods A cross-sectional telephone survey was conducted in 2019 on Chinese adults aged 18-74 (n = 3200). Respondents were asked about various past-year first-hand drinking harms (after one's own drinking), second-hand harms (harms from other people's drinking) and views of neighbourhood alcohol outlet regulation. Results Of drinkers, 21.1% reported first-hand alcohol harms, with physical/mental health harms (15.7%) most commonly reported. Younger-aged drinkers (adjusted odds ratios [AOR] 2.64, 95% confidence interval [CI] 1.63, 4.48) and heavy drinkers (AOR 2.34, 95% CI 1.55, 3.55) were more likely to report first-hand harms. Of the sample, 18.2% experienced past-year second-hand harms, with public harms (12.9%) most commonly reported. Young age (AOR 1.88, 95% CI 1.43, 2.49), higher education (AOR 1.44, 95% CI 1.13, 1.83), past-year binge drinking (AOR 4.29, 95% CI 3.04, 6.05) and communal living (AOR 2.04, 95% CI 1.13, 3.75) predicted greater likelihood of second-hand alcohol harms. Higher neighbourhood alcohol outlet density was not associated with any first-hand harms and only significantly predicted being inconvenienced by drinkers. Although victims of second-hand alcohol harms were more supportive of regulating outlet density, 93.3% of respondents were opposed to such policies. Discussion and conclusions Although high levels of alcohol-related harms were not reported by Hong Kong adults, regulations should target young drinkers and binge drinkers who are most likely to experience drinking-related harms.

The built-in electric field generated by polar materials is one of the most effective strategies to promote the separation of photogenerated electron-hole pairs in the field of photocatalysis. However, because of the complexity and diversity of the built-in electric field in polar materials, it is not clear how to enhance the photocatalytic performance and how to control the polar electric field effectively. To this end, four-layered bismuth oxyhalides, BiOX, and BiOXO3 (X = Br, I) were synthesized by a simple hydrothermal method. X-ray diffraction, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy analysis confirmed that they all have the structure characteristics of a sillenite phase. Scanning electron microscopy images show that they all have the morphology of nanosheets. Among them, BiOBrO3 was successfully synthesized and characterized for the first time in the present work. The order of photocatalytic performance (including carrier's lifetime, photocurrent density, and H2 evolution rate) of the four compounds is listed as follows: BiOBrO3 > BiOI > BiOIO3 > BiOBr. In the bulk of the BiOXO3 photocatalyst, the spontaneous polar built-in electric field along the [001] direction is the crucial factor to inhibit the recombination of photogenerated electron-hole pairs, while the surface polar electric field in BiOI can outstandingly inhibit the recombination of photogenerated electron-hole pairs due to the breaking of the mirror symmetry. Therefore, regulating the microstructure and composition of the structure unit, which generates the built-in electric field, can indeed control the magnitude, direction, and effects of built-in electric fields. In practice, we should carefully adjust the strategy according to the actual situation so as to reasonably design and use the polar electric field, giving full play to its role and enhancing the photocatalytic performance.

MicroRNAs, as a group of post-transcriptional regulators, regulate multiple pathological processes including metastasis during tumor development. Here, we demonstrated the metastasis-suppressive function of microRNA (miR)-338-5p in esophageal squamous cell carcinoma (ESCC). Overexpression of miR-338-5p had inhibitory effect on invasive ability of ESCC cells and extracellular matrix degradation, whereas silencing miR-338-5p had opposite effects. Mechanistically, miR-338-5p directly targeted the 3′ untranslated regions of hepatocellular growth factor receptor cMet (cMET) and epidermal growth factor receptor (EGFR). As a result, miR-338-5p inhibited the downstream signaling cascades of cMET and EGFR and repressed cMET- and EGFR-mediated ESCC cell invasion. Re-expression of cMET or EGFR in miR-338-5p overexpressing ESCC cells was sufficient to derepress ESCC cell invasion both in vitro and in vivo. We further showed that such manipulation downregulated the expression and secretion of matrix metalloproteinases 2 and 9, which resulted in impaired extracellular matrix degradation and cell invasion. Most importantly, systemic delivery of miR-338-5p mimic significantly inhibited metastasis of ESCC cells in nude mice. Taken together, our results uncovered a previously unknown mechanism through which miR-338-5p suppresses ESCC invasion and metastasis by regulating cMET/EGFR-matrix metalloproteinase 2/9 axis and highlighted the potential significance of miR-338-5p-based therapy in treating patients with metastatic ESCC.

Remifentanil is a potent, short-acting opioid analgesic drug that can protect tissues from ischemia and reperfusion injury though anti-inflammatory effects. However, the utility of remifentanil in liver regeneration after hepatectomy is not known. Using a 70% hepatectomy mouse model (PHx), we found that preconditioning animals with 4 μg/kg remifentanil enhanced liver regeneration through supporting hepatocyte proliferation but not through anti-inflammatory effects. These effects were also phenocopied in vitro where 40 mM remifentanil promoted the proliferation of primary mouse hepatocyte cultures. We further identified that remifentanil treatment increased the expression of β-arrestin 2 in vivo and in vitro. Demonstrating specificity, remifentanil preconditioning failed to promote liver regeneration in liver-specific β-arrestin 2 knockout (CKO) mice subjected to PHx. While remifentanil increased the expression of activated (phosphorylated)-ERK and cyclin D1 in PHx livers, their levels were not significantly changed in remifentanil-treated CKO mice nor in WT mice pretreated with the ERK inhibitor U0126. Our findings suggest that remifentanil promotes liver regeneration via upregulation of a β-arrestin 2/ERK/cyclin D1 axis, with implications for improving regeneration process after hepatectomy.

Gas-phase fluidized-beds reactor (FBR) can overcome the shortages of bed clogging and performance decline in packed-bed reactors on VOCs treatment. Ideal FBR packing materials with minimum fluidized velocity and surface characteristics are required. In this study, an expanded polystyrene (EPS) with particle size 1.0–2.0 mm was selected as the skeleton among six types of EPS and two types of expanded polypropylene (EPP). They were then physically coated with a combination of potato dextrose medium, fine wheat bran particles, and inorganic glue. Different glue concentrations and amounts of medium were tested and the optimal values of 2 % and 0.22 g∙cm−2 were achieved. The wheat-coated EPS obtained hydrophilic functional groups on the surface, and its contact angle decreased from 93° to 37° after coating. By scanning electronic microscopy, more microorganisms were observed on the surface of the coated EPS than that of the uncoated EPS. A lab-scale fluidized bioreactor was built to treat gaseous ethanol. The minimum fluidized velocity of coated packing materials was 0.2 m∙s−1 under a relative humidity of 50 ± 10 %, reaching an average elimination capacity of 681 g m-3 h−1 during the 28-days operation, while the bioreactor packed with uncoated EPS reached only 18 g m−3 h−1.

As part of the inner ear, the vestibular system is responsible for sense of balance, which consists of three semicircular canals, the utricle, and the saccule. Increasing evidence has indicated that the noncanonical Wnt/PCP signaling pathway plays a significant role in the development of the polarity of the inner ear. However, the role of canonical Wnt signaling in the polarity of the vestibule is still not completely clear. In this study, we found that canonical Wnt pathway-related genes are expressed in the early stage of development of the utricle and change dynamically. We conditionally knocked out β-catenin, a canonical Wnt signaling core protein, and found that the cilia orientation of hair cells was disordered with reduced number of hair cells in the utricle. Moreover, regulating the canonical Wnt pathway (Licl and IWP2) in vitro also affected hair cell polarity and indicated that Axin2 may be important in this process. In conclusion, our results not only confirm that the regulation of canonical Wnt signaling affects the number of hair cells in the utricle but also provide evidence for its role in polarity development.

In order to further understanding of how alga are adjusted to chromium(VI) toxicity at the level of photosynthesis, the pigment content and chlorophyll a (Chla) fluorescence parameters, were studied in Macrocystis pyrifera blades treated with 0, 0.5, 2, 10 and 20 mg/L Cr (VI) solution for 24 h. Results showed that these parameters were clearly affected by different concentrations of Cr (VI The pigment contents and Chla fluorescence parameters were clearly decreased in M. pyrifera exposed to 20 mg/L Cr (VI). Furthermore, the present study provided novel insights into Cr(VI) toxicity at the proteomic level using TMT-based technology after M. pyrifera was irrigated with 0 or 20 mg/L Cr(VI) solution for 24 h. The decreases in pigment content and Chl a fluorescence parameters resulted from alternations of the related proteins involved in pigment synthesis and photosynthetic processes. Expression of 227 different proteins was detected. Analysis of significant changes in KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways showed that M. pyrifera is able to reorganize its proteome in favor of photosynthesis, carbon fixation, metabolic pathways, oxidative phosphorylation, biosynthesis of amino acids, carbon metabolism, ribosome and biosynthesis of secondary metabolites under Cr(VI) stress. These findings could provide valuable information to elucidate the mechanism of Cr(VI) toxicity in M. pyrifera.

This study aimed to explore the quantitative efficacy of L-carnitine supplementation on glycemic control in type 2 diabetes mellitus patients using model-based meta-analysis (MBMA).Literatures were retrieved from the public database and data from these trials were extracted. The quantitative efficacy of L-carnitine on fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) in type 2 diabetes mellitus patients were evaluated by maximal effect (EIn the model of FPG, EIt was the first time to provide valuable quantitative information for efficacy of L-carnitine supplementation on glycemic control in type 2 diabetes mellitus patients.

An electrocatalytic carbon dioxide reduction reaction (CO2RR) is an appealing route to obtain the value-added feedstocks and alleviate the energy crisis. However, how to achieve high-performance electrocatalysts for CO2 reduction to formate is challenging owing to the poor intrinsic activity, insufficient conductivity, and low surface density of active sites. Herein, we fabricated an extremely active and selective hydrangea-like superstructured micro/nanoreactor of ultrathin bismuth nanosheets through an in situ electrochemical topotactic transformation of hierarchical bismuth oxide formate (BiOCOOH). The resulted bismuth nanosheet superstructure is in the form of three-dimensional intercrossed networks of ultrathin nanosheets, forming an ordered open porous structure through self-assembly, which can be used as a micro/nanoreactor to enable a large electrochemically active surface area as well as high atomic utilization. Such a distinctive nanostructure endows the material with high electrocatalytic performances for CO2 reduction to formate with near-unity Faradaic selectivity (>95%) in a wide potential window from -0.78 to -1.18 V. Furthermore, this micro/nanoreactor can give the high current densities over 300 mA cm-2 at low applied potentials without compromising selectivity in a flow cell reactor. Density functional theory (DFT) and in situ attenuated total reflection-infrared spectroscopy (in situ ATR-IR) were further conducted to interpret the CO2RR mechanisms.

Liang Zhang, Shilin Xiao, Xun Kang, Tao Sun, Chunyu Zhou, Zhongsheng Xu, Mengmeng Du, Ya Zhang, Guangxian Wang, Yun Liu, Dong Zhang, Mingfu Gong Department of Radiology, Xinqiao Hospital, Army Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Dong Zhang; Mingfu GongDepartment of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao Street, Shapingba District, Chongqing, People’s Republic of ChinaTel +86 2368763843Fax +86 2368755306Email hszhangd@163.com; hummer198625@163.comBackground: Manganese Ferrite Nanoparticles (Mn-IONPs) are widely used in biomedical field and their cytotoxicity has been initially explored, but the mechanism remains obscure. The nano-bio interactions are believed to be crucial for cytotoxicity mechanism, while little data have been acquired.Methods: Mn-IONPs were synthesized by thermal decomposition of acetylacetonate precursor. After physicochemical characterization, we analyzed the metabolic conversion and removal of Mn-IONPs in RAW264.7 cells by Prussian blue staining, TEM, HRTEM and elemental quantitative analysis, followed by gene expression evaluation using quantitative RT-PCR.Results: Mn-IONPs were successfully synthesized. Both the uptake and cytotoxicity of Mn-IONPs on RAW264.7 cells were time- and dose-dependent. After internalized, Mn-IONPs were passed to daughter cells with passages on. Meanwhile, Mn-IONPs were exocytosed and digested to metal ions and further excreted out, resulted in the labeling rate and ions contents decreased gradually. As ion influx related genes, the expressions of ZIP14, IRP2, FtH and DMT1 were suppressed within 24 hours but overexpressed to a plateau at the 48th hour in a dose-dependent manner. At the 72nd hour, ZIP14 and DMT1 mRNA levels decreased toward normal, while IRP2 and FtH kept up-regulated. As efflux related genes, FPN, SLC30A10 and Hamp2 genes were up-regulated within 24– 72 hours; SPCA1 was suppressed at the 24th and 72nd hour, while overexpressed at the 48th hour. All the efflux related genes’ mRNA had a dose-dependent increasing manner at the corresponding time points.Conclusion: Mn-IONPs showed time- and dose-dependent cytotoxicity and cell labeling rate in RAW264.7 cells. Accompanying with the intracellular catabolic breakdown and exocytosis of Mn-IONPs, RAW264.7 cells also secreted and re-uptook manganese and iron ions to maintain intracellular homeostasis in the succeeding passages. And the metabolic conversion of Mn-IONPs in RAW264.7 cells can affect the expression of ZIP14, DMT1, FPN, SLC30A10, IRP2, FtH, Hamp2 and SPCA1 genes.Keywords: manganese ferrite nanoparticles, cytotoxicity, metabolism, metal transporter genes, RAW264.7 macrophage cells

T helper (Th) 2 cell-medicated immune response participates in various immune diseases, including systemic lupus erythematosus (SLE). Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to be associated with T helper 2 (Th2) cell activation. Here, we demonstrated the molecular mechanism of NEAT1 in regulating Th2 cell activation. We found that NEAT1 was located in nucleus. NEAT1 overexpression promoted the levels of Th2-related cytokines IL-4, IL-5 and IL-13 in CD4+ T cells. Moreover, NEAT1 up-regulation reduced Th1-related cytokine INF-γ production and enhanced the levels of Th17-related cytokines IL-17 in CD4+ T cells. STAT6 deficiency reduced the levels of IL-4, IL-5, IL-13 and IL-17 enhanced the levels of INF-γ in CD4+ T cells, which was rescued by NEAT1 overexpression. Moreover, NEAT1 promoted STAT6 protein expression, whereas NEAT1 had no effect on the expression of STAT6 mRNA. Furthermore, NEAT1 interacted with STAT6, inhibited the ubiquitination of STAT6 in CD4+ T cells. In conclusion, our work has confirmed that NEAT1 promotes STAT6 expression by inhibiting STAT6 ubiquitination, thereby promoting Th2 cell activation. Thus, our work may highlight novel insights into the molecular mechanism of NEAT1 in regulating Th2 cell activation.

A new, efficient approach toward the preparation of 2-aryl-2,3-dihydrobenzofuran scaffolds through the Cu/SPDO-catalyzed [3 + 2] cycloaddition between quinone ester and styrene derivatives has been developed. The procedure features excellent enantioselectivities (up to 99% ee), high yields (up to 96%), and broad substrate tolerance. Additionally, asymmetric synthesis of natural corsifurans A and B from commercially available starting materials has also been achieved in two or three steps using this reaction as a key transformation.

Oxidative stress, the renin-angiotensin system (RAS), and inflammation are some of the mechanisms involved in the pathogenesis of hypertension. The aim of this study is to examine the protective effect of the chronic administration of astaxanthin, which is extracted from the shell of crabs and shrimps, into hypothalamic paraventricular nucleus (PVN) in spontaneously hypertensive rats. Animals were randomly assigned to 2 groups and treated with bilateral PVN infusion of astaxanthin or vehicle (artificial cerebrospinal fluid) through osmotic minipumps (Alzet Osmotic Pumps, Model 2004, 0.25 μL/h) for 4 weeks. Spontaneously hypertensive rats had higher mean arterial pressure and plasma level of norepinephrine and proinflammatory cytokine; higher PVN levels of reactive oxygen species, NOX2, NOX4, IL-1β, IL-6, ACE, and AT1-R; and lower PVN levels of IL-10 and Cu/Zn SOD, Mn SOD, ACE2, and Mas receptors than Wistar-Kyoto rats. Our data showed that chronic administration of astaxanthin into PVN attenuated the overexpression of reactive oxygen species, NOX2, NOX4, inflammatory cytokines, and components of RAS within the PVN and suppressed hypertension. The present results revealed that astaxanthin played a role in the brain. Our findings demonstrated that astaxanthin had protective effect on hypertension by improving the balance between inflammatory cytokines and components of RAS.

A chemical investigation of Sigesbeckia glabrescens Makino identified four compounds. On the basis of spectroscopic data, they were determined to be ent-pimarane-type diterpenoids and their analogu...

Surface-enhanced Raman spectroscopy (SERS) is an optical technique for molecule identification. However, fabrication of flexible and structured SERS substrates for performance improvement in a facile and cost-effective manner is challenging. In this work, we reported a polytetrafluoroethylene (PTFE)-based flexible SERS substrate by femtosecond laser direct writing (FsLDW) technology. The femtosecond laser-treated PTFE surface is 3D hierarchical micro-/nano-structures, and the structured PTFE-based SERS chip shows excellent performance enhancement. As a result, 10−7 M can be detected, which shows excellent potentials in developing flexible SERS for wearable electronics.

The electrochemical CO2 reduction reaction (CO2RR) to value-added and readily collectable liquid products is promising but remains a great challenge due to the lack of efficient and robust electrocatalysts. Herein, a self-supported large-size three-dimensional porous conductive network of bismuthene (Bi-ene-NW) as an efficient superstructured electrocatalytic membrane (ECM) has been pioneeringly assembled, in which the atomically thin Bi-ene with rich edge-site-involved defects is interconnected, highly exposing the active sites. Such ECM can be utilized as an ascendant catalytic cathode, displaying an unprecedented CO2RR performance with near-unity selectivity in a wide potential window and large current density for formate production. Remarkably, when integrated into a gas diffusion electrode (GDE) in a flow cell, Bi-ene-NW was capable of delivering industry-compatible current densities up to 560 mA cm−2 for formate production. Moreover, it was ultrastable to continuously operate for over 500 h at a high current density without significant activity decay. Such outstanding performance should be inseparable from its abundant accessible sites with high intrinsic activity, multiple interconnected channels and superior conductivity for mass/charge transport. The operando ATR-IR and theoretical calculations further deciphered that the rich defects in the roughened plane edges and in-plane pore edges of Bi-ene are conducive to the *OCHO intermediate stabilization.

A novel spiro-pyrrolidine (SPD)-derived bifunctional thiourea catalyst has been developed, enabling the development of a stereoselective conjugate addition of furfurals to β,γ-unsaturated α-ketoesters. The reaction represents an example of asymmetric trienamine catalysis in the benzylic C–H functionalization of 5-benzylfurfurals, and the rigid spirocyclic framework of the catalyst is proven to be essential for a highly enantioselective transformation.

Herein, for the first time, an active and stable bifunctional electrocatalyst has been elaborately designed to achieve the integration of CO2 reduction and anodic non-classical reaction to efficiently yield products of high value at both electrodes, which was constructed by surface anchoring of a novel multi-azido-group-bearing nickel phthalocyanine onto carbon nanotubes at the single-molecule level via strong interactions. Concretely, the obtained heterojunction-type electrocatalyst exhibits ultrahigh activity for completely selective CO2-to-CO conversion with a 100% faradaic efficiency in a wide potential window, large partial current density (>200 mA cm−2) and turnover frequency, and remarkable stability. Particularly, a mass of azido-derived amine groups around the nickel phthalocyanine centers increase the local concentration of CO2via chemisorption, thus boosting the formation of the key intermediate. Unprecedentedly, an exotic electrolytic system integrating CO2 reduction with oxidative nano-polymerization was further conceptually developed using this individual bifunctional electrocatalyst for both the cathode and anode. Besides the high-performance CO2 reduction at the cathode, a unique porous 3D polymer nano-framework was obtained in the anode chamber instead of low-value O2, while the cell voltage was significantly reduced by 1.05 V to achieve 10 mA cm−2.

Rationale: Little is known about the roles of proteoglycans in esophageal cancer. This study aims to investigate the roles and mechanisms of serglycin (SRGN) proteoglycan in promoting metastasis of esophageal squamous cell carcinoma (ESCC). Methods: Reverse phase protein array analysis was used to identify activated signaling pathways in SRGN-overexpressing cells. Chemokine array was used to identify differentially secreted factors from SRGN-overexpressing cells. Binding between SRGN and potential interacting partners was evaluated using proximity ligation assay and co-immunoprecipitation. The glycosaminoglycan (GAG) chains of SRGN were characterized using fluorophore-assisted carbohydrate electrophoresis. Tissue microarray and serum samples were used to determine the correlation of SRGN expression with clinicopathological parameters and patient survival. Results: In vitro and in vivo experiments showed that SRGN promoted invasion and metastasis in ESCC via activating ERK pathway, stabilizing c-Myc and upregulating the secretion of matrix metalloproteinases. SRGN-knockdown suppressed tumorigenic hallmarks. These SRGN-elicited functions were carried out in an autocrine manner by inducing the secretion of midkine (MDK), which was further identified as a novel binding partner of SRGN for the formation of a SRGN/MDK/CD44 complex. In addition, SRGN interacted with MDK and matrix metalloproteinase 2 in ESCC via its GAG chains, which were mainly decorated with chondroitin sulfate comprising of ∆di-4S and ∆di-6S CS. Clinically, high expression of serum SRGN in serum of patients with ESCC was an independent prognostic marker for poor survival. Conclusions: This study provides the first evidence that elevated serum SRGN has prognostic significance in patients with ESCC, and sheds light on the molecular mechanism by which elevated circulating SRGN in cancer patients might promote cancer progression.

A multi-binding site chemosensor, N-(3-methoxy-2-hydroxybenzylidene)-3-hydroxy-2-naphthahydrazone (H3L), with excited-state intramolecular proton transfer (ESIPT) behaviour was prepared and characterized. It possesses no aggregation-induced emission (AIE) characteristics but can detect Cd2+ and Zn2+ ions selectively in the "off-on" mode based on the AIE of their complexes in the media of THF/HEPES and THF/H2O, respectively, which will provide a new strategy for target detection based on AIE. The detection limits of Zn2+ and Cd2+ were 9.85 × 10-9 M and 1.27 × 10-7 M, respectively. The aggregates of the complexes formed in the detection system were confirmed by DLS data and SEM images. The corresponding Zn2+ (1) and Cd2+ (2) complexes were prepared to investigate the response mechanism. Powder X-ray diffraction and single crystal X-ray diffraction proved that complex 1 is the species formed in the detection system. The chemosensor coordinates with the Cd2+ and Zn2+ ions in different formation and coordination modes, leading to the emission position of the aggregates at 560 and 645 nm, respectively, based on which Cd2+ ions were successfully differentiated from Zn2+ ions. Moreover, the detection of Cd2+ and Zn2+ ions was realized qualitatively via test paper and quantitatively in water.

Designing electrically conductive electrode material with a hierarchical pore structure from abundant raw material remains a significant challenge in the development of energy storage research. In this work, 3D porous carbons with high surface areas are synthesized via high-temperature carbonization and activation. The synthesized activated carbons deliver a specifical capacitance of 280 F g−1 and area-specific capacitance of 1.3 F cm−2 at a current density of 0.5 A g−1. The assembled symmetric supercapacitor can deliver a high energy output (7.7 Wh kg−1 at 5200 W kg−1). Thus, it is demonstrated the repurposing of lignin waste as electrode material can be a feasible resource that goes beyond the limitations of utilizing lignin in low value-added applications.

Intratympanic injection of gentamicin has proven to be an effective therapy for intractable vestibular dysfunction. However, most studies to date have focused on the cochlea, so little is known about the distribution and uptake of gentamicin by the counterpart of the auditory system, specifically vestibular hair cells (HCs). Here, with a combination of in vivo and in vitro approaches, we used a gentamicin-Texas Red (GTTR) conjugate to investigate the mechanisms of gentamicin vestibulotoxicity in the developing mammalian utricular HCs. In vivo, GTTR fluorescence was concentrated in the apical cytoplasm and the cellular membrane of neonatal utricular HCs, but scarce in the nucleus of HCs and supporting cells. Quantitative analysis showed the GTTR uptake by striolar HCs was significantly higher than that in the extrastriola. In addition, the GTTR fluorescence intensity in the striola was increased gradually from 1 to 8 days, peaking at 8-9 days postnatally. In vitro, utricle explants were incubated with GTTR and candidate uptake conduits, including mechanotransduction (MET) channels and endocytosis in the HC, were inhibited separately. GTTR uptake by HCs could be inhibited by quinine, a blocker of MET channels, under both normal and stressed conditions. Meanwhile, endocytic inhibition only reduced GTTR uptake in the CoCl2 hypoxia model. In sum, the maturation of MET channels mediated uptake of GTTR into vestibular HCs. Under stressed conditions, MET channels play a pronounced role, manifested by channel-dependent stress enhanced GTTR permeation, while endocytosis participates in GTTR entry in a more selective manner.

Congli Jia,1 Zhengquan Li,2 Dong Guo,1 Zhen Zhang,3 Jingming Yu,4 Guangdong Jiang,1 Xiaobo Xing,3 Shengjun Ji,5 Feng Jin3 1Weifang Medical University, Weifang, People’s Republic of China; 2Department of Laboratory Pathology, People’s Liberation Army 80th Group Military Hospital, Weifang, People’s Republic of China; 3Department of Radiotherapy & Oncology, Qingdao Center Hospital, Qingdao, People’s Republic of China; 4Department of Radiotherapy & Oncology, Shandong Hospital, Jinan, People’s Republic of China; 5Department of Radiotherapy & Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, People’s Republic of ChinaCorrespondence: Shengjun JiDepartment of Radiotherapy & Oncology, Nanjing Medical University Affiliated Suzhou Hospital, No. 16 Baita Road, Suzhou 215001, People’s Republic of ChinaEmail drshengjunji@163.comFeng JinDepartment of Radiotherapy & Oncology, Qingdao Center Hospital, No. 127 Siliu Road, Qingdao 266042, People’s Republic of ChinaEmail 1093910079@qq.comBackground: Brain metastases (BM) are severe incidents among patients with non-small cell lung cancer (NSCLC) and have been associated with significant morbidity and decreased survival; thus, new methods are required to improve clinical management. Magnetic resonance spectroscopy (MRS) allows noninvasive measurements of biochemical information from tumor tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to explore the application of MRS in the assessment of tumor prognosis after stereotactic radiotherapy in NSCLC patients with BM.Patients and Methods: MRS was performed on NSCLC patients attending Qingdao Center Hospital with suspected BM, and 68 patients were included in the survival analysis. The qualitative and quantitative parameters of MRS metabolites, such as choline (Cho), creatine (Cr), and N-acetyl-aspartate (NAA), were recorded. To select a cutoff for MRS metabolite parameters in the tumor and to distinguish patients who had recurrence, we performed an ROC curve analysis. Univariate and multivariate Cox regression analyses were used to assess the association between MRS metabolite parameters and clinical cancer prognosis.Results: The average age was 56 years. A total of 68 NSCLC patients underwent metabolic evaluation with single voxel proton MRS and were selected for retrospective analysis. According to the area under the curve (AUC) to predict recurrence, the MRS metabolite parameters were determined as Cho (AUC=0.550), Cr (AUC=0.415), NAA (AUC=0.524), NAA/Cr (AUC=0.600), Cho/Cr (AUC=0.723), and Cho/NAA (AUC=0.543). Cho and Cr predicted poor survival while Cho/Cr and NAA/Cr predicted improved survival (P< 0.05). In the multivariate model with adjustment to establish the potential role of MRS metabolite parameters, Cho/Cr showed a significant association with OS (P=0.009) and PFS (P=0.006) after stereotactic radiotherapy.Conclusion: The positive results of this study indicate the predictive value of metabolic characteristics of BM detected with MRS for the outcome after stereotactic radiotherapy.Keywords: brain metastases, magnetic resonance spectroscopy, stereotactic radiotherapy

Berberine, as a representative isoquinoline alkaloid, exhibits significant hypolipidemic activity in both animal models and clinical trials. Recently, a large number of studies on the lipid-lowering mechanism of berberine and studies for improving its hypolipidemic activity have been reported, but for the most part, they have been either incomplete or not comprehensive. In addition, there have been a few specific reviews on the lipid-reducing effect of berberine. In this paper, the physicochemical properties, the lipid-lowering mechanism, and studies of the modification of berberine all are discussed to promote the development of berberine as a lipid-lowering agent. Subsequently, this paper provides some insights into the deficiencies of berberine in the study of lipid-lowering drug, and based on the situation, some proposals are put forward.

Ruthenium (Ru) is a promising element to heighten the comprehensive mechanical properties of TiAl alloys. In the present study, the phase transformation during the cooling of Ti-47Al-2Cr-2Nb-xRu (x=0, 0.1, 0.5, 1.0, at.%) alloys was investigated. The results show that Ru tends to segregate in the interdendritic region during solidification, and therefore, refines the as-cast microstructure of the alloys. As a β-stabilizer, Ru does not induce a novel solidification reaction but maintains the peritectic reaction of L+β→α. An excessive Ru content would cause the formation of (γ+τ1+B2) and (α+γ+τ1+B2) phase regions below 1,250 °C. The precipitation of τ1-containing mixture is attributed to the Ru-segregation, which inhibits the reaction of α→γ and facilitates the formation of B2 phase. The discontinuous coarsening of γ phase and block τ1 phase formed alternately in a manner of analogous eutectoid decomposition within B2 phase. In addition, the effect of Ru content on compression property of the alloys was studied. The yield strength increases up to 427 MPa at 800 °C with the addition of 1.0at.% Ru, which is mainly due to the solution strengthening effect of Ru.

The Fe reduction, microstructure evolution and corrosion susceptibility of Mg−Mn alloys made from magnesium scrap refining with Mn addition were investigated. The results show that significant Fe content change occurs during near-solid-melt treatment (NSMT) process even in the absence of Mn, because of the high saturation of Fe in the melt. Furthermore, in the NSMT process, even a small amount of Mn addition can lead to a sharp deposition of Mn atoms. The NSMT process can increase the growth rate of the Fe-rich particles, and then accelerate their sinking movement. Nevertheless, the addition of Mn hinders the coarsening process of Fe-rich particles. Besides, the corrosion susceptibility of the alloys is mainly affected by the solubility of Fe, which can be significantly reduced by Mn addition. Moreover, the presence of more Fe-rich particles does not necessarily increase the corrosion susceptibility of the alloy. Consequently, in the refining process of Mg−Mn alloys made from magnesium scrap, on the basis of NSMT process and adding an appropriate Mn content (about 0.5 wt.%), the purity of the melt can be improved, thereby obtaining an alloy with excellent corrosion resistance.

Rational manipulation of supramolecular structures on surfaces is of great importance and challenging. We show that imidazole-based hydrogen-bonded networks on a metal surface can transform into an isostructural coordination network for facile tuning of the pore size and guest recognition behaviours. Deposition of triangular-shaped benzotrisimidazole (H3btim) molecules on Au(111)/Ag(111) surfaces gives honeycomb networks linked by double N–H⋯N hydrogen bonds. While the H3btim hydrogen-bonded networks on Au(111) evaporate above 453 K, those on Ag(111) transform into isostructural [Ag3(btim)] coordination networks based on double N–Ag–N bonds at 423 K, by virtue of the unconventional metal–acid replacement reaction (Ag reduces H+). The transformation expands the pore diameter of the honeycomb networks from 3.8 Å to 6.9 Å, giving remarkably different host–guest recognition behaviours for fullerene and ferrocene molecules based on the size compatibility mechanism., A hydrogen-bonded network on a Ag(111) surface can transform into an isostructural Ag(i) coordination network, giving drastically different host–guest recognition behaviours.

Berberine (BBR), a well-known alkaloid, exhibits various pharmacological activities, especially hypolipidemic activity, which has attracted much interest from medicinal chemists in the past decade. However, little progress was made on the structural modification of BBR for improving lipid-lowering activity, mainly due to its unclear biological target and low safety. In this study, a new scaffold of 7,9-disulfatetrahydroberberine was discovered unexpectedly, provided with extremely low cytotoxicity. Hence, a novel series of highly safe 7,9-disulfatetrahydroberberines were designed, synthesized, and evaluated for their hypolipidemic activities. In order to investigate the significance of the 9-position substituent, another new series of 7-sulfatetrahydroberberines were designed and synthesized. Lipid-lowering experiments showed that among these compounds, 5f exhibited the best lipid-lowering activity based on two cell models, 3T3-L1 cells and HepG2 cells. Compared with the blank control, the inhibition rate of compound 5f against total cholesterol was over 60%, the inhibition rate against triglyceride was over 70%, the inhibition rate against low-density lipoprotein cholesterol was approximately 75%, and the inhibition rate against high-density lipoprotein cholesterol was close to 50%, which were far superior to the positive control BBR. This result also verified the feasibility of the development of BBR as a lipid-lowering drug via disubstituted modification at the 7- and 9-position.

The inhibition of 5-α reductase type 2 (SRD5A2) by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement (BPE). Certain BPE patients showing no SRD5A2 protein expression are resistant to finasteride therapy. Our previous work showed that methylated cytosine-phosphate-guanine (CpG) islands in the SRD5A2 gene might account for the absence or reduction of SRD5A2 protein expression. Here, we found that the expression of the SRD5A2 protein was variable and that weak expression of the SRD5A2 protein (scored 0-100) occurred in 10.0% (4/40) of benign adult prostates. We showed that the expression of SRD5A2 was negatively correlated with DNA methyltransferase 1 (DNMT1) expression. In vitro SRD5A2-negative BPH-1 cells were resistant to finasteride treatment, and SRD5A2 was re-expressed in BPH-1 cells when SRD5A2 was demethylated by 5-Aza-2'-deoxycytidine (5-Aza-CdR) or N-phthalyl-L-tryptophan (RG108). Furthermore, we determined the exact methylation ratios of CpG dinucleotides in a CpG island of SRD5A2 through MassArray quantitative methylation analysis. Ten methylated CpG dinucleotides, including four CpG dinucleotides in the promoter and six CpG dinucleotides in the first exon, were found in a CpG island located from -400 bp to +600 bp in SRD5A2, which might lead to the silencing of SRD5A2 and the absence or reduction of SRD5A2 protein expression. Finasteride cannot exert a therapeutic effect on patients lacking SRD5A2, which may partially account for the resistance to finasteride observed in certain BPE patients.

Background Lingual linear lesions (LLLs) are the oral linear lesions located on the dorsum, lateral borders, and/or ventral surface of tongue. It has been suggested that LLLs might be an early clinical sign of vitamin B12 deficiency. Here, a retrospective study was conducted to further investigate and validate the association between LLL and vitamin B12 deficiency. Methods Based on the clinical examination, patients with LLLs were enrolled and analyzed retrospectively. Data regarding clinical and laboratory features were obtained. Follow-up was done at least 6 months following appropriate supplementation therapy. Results A total of 57 patients, consisting of 20 males and 37 females with a mean age of 59.12 years (range, 18-80), were enrolled in this study. The hematological examination revealed that 56 (98.25%) of the 57 patients had severe serum vitamin B12 deficiency, and the other 1 patient had a borderline low level of vitamin B12 . All the enrolled patients responded well to cobalamin replacement therapy. Conclusion LLLs might be a clinical sign strongly suggestive of severe vitamin B12 deficiency.