Glucose-sensitive poly(ether sulfone) composite membranes blended with phenylboronic acid-based amphiphilic block copolymer for self-regulated insulin release.

Glucose-sensitive membranes have promising applications in insulin release. Phenylboronic acid (PBA) is an important glucose reporter. Most of PBA-based glucose-sensitive materials are expansion-type, which cannot act as chemical valves in porous membranes for self-regulated insulin release. In this study, a glucose-sensitive membrane with PBA-based contraction-type amphiphilic block copolymer polystyrene-b-poly(N-isopropylacrylamide-co-2-(acrylamido) phenylboronic acid) (PSNB) as chemical valves was constructed through non-solvent induced phase separation (NIPS) method. Due to surface segregation, hydrophobic polystyrene (PS) component can anchor in the membrane matrix to improve the stability of the membrane, and glucose-sensitive hydrophilic poly(N-isopropylacrylamide-co-2-(acrylamido) phenylboronic acid) (PNB) component can expose on the surfaces of the membrane and the channels to provide glucose-sensitivity of the membrane. With increasing the polymer content or chain length of the hydrophilic component, the glucose sensitivity of the membrane was improved. The blend membrane showed glucose-sensitive insulin release behavior in simulated body fluids (SBF) and fetal bovine serum (FBS). The membrane also exhibited good antifouling properties and biocompatibility.

Gastrointestinal bleeding caused by metastatic testicular choriocarcinoma: a case report and literature review.

BACKGROUND: Testicular tumor is one of the common solid tumors in young men. Testicular choriocarcinoma is a non-spermatogonial germ cell tumor, which is the rarest of all testicular cancers. Choriocarcinoma usually shows bleeding at the metastatic site, while gastrointestinal involvement is rare. METHODS: Here, we report a case of testicular choriocarcinoma with gastrointestinal bleeding as the first diagnosis and summarize the similar cases all over the world in recent 20 years. RESULTS: A 28-year-old male was treated with repeated melena for 2 months. No bleeding foci of the stomach, duodenum, colon, and rectum were found in endoscopy, and no bleeding foci of digestive tract was found in selective angiography, but a space occupying lesions of the lung, liver, and upper jejunum were found in chest and abdominal CT. Considering the possibility of a metastatic tumor and the ineffectiveness of medical treatment, the patient was converted to surgical treatment. The postoperative pathology was consistent with testicular choriocarcinoma. The patient received a chemotherapy regimen of paclitaxel, ifosfamide, and cisplatin. At present, the chemotherapy regimen is well tolerated. CONCLUSIONS: The case report confirmed that even if we cannot find the logical relationship between clinical manifestations and genital examination, genital examination should also be part of the patient's systematic examination.

New terpenoids and triketides from culture of the fungus Botrysphaeria laricina.

Three new isopimarane-type diterpenoids, botrysphins G-I (1-3), a new muurolane-type sesquiterpenoid, 11,12-dihydroxylentideusether (4), and two new triketides, 4-dechlorobotrysphone C (5) and 4,5-dihydroxy-3-methoxy-6-undecanoyloxy-2-cyclohexen-1-one (6), together with one known diterpenoid, sphaeropsidin A (7), one sesquiterpenoid, lentideusether (8), and one triketide sphaeropsidone (9), were isolated from culture of the fungus Botrysphaeria laricina associated with the moss Rhodobryum umgiganteum. The structures of the new compounds were established on the basis of extensive spectroscopic techniques including HRMS and 1D and 2D NMR data. Compounds 1 and 2 exhibited NO inhibitory activity with IC50 values of 13.9 µM and 41.9 µM, respectively. At the same time, these two compounds showed quinone reductase inducing activity with 2.7-fold of induction for 1 at 12.5 µM and 1.6-fold for 2 at 25.0 µM.

Modulation of the transport properties of metal/MoS2 interfaces using BN-graphene lateral tunneling layers.

Modulating the n- and p-type interfacial charge transport properties of the metal-semiconductor interface is vital to realizing high performance two-dimensional material nanodevices and is still a significant challenge. Here, a boron nitride (BN)-graphene lateral heterostructure (LH) was used as the interfacial tunneling layer to control the Schottky barrier, Fermi level pinning and charge injection efficiency of the metal-MoS2 interface. The BN-graphene LH with graphene-N junction structure decreased the n-type vertical Schottky barrier and enhanced the interfacial tunneling probability, while the graphene-B junction structure decreased the p-type vertical Schottky barrier. Consequently, the n-type Au/LH-MoS2 interface with Ohmic character and high tunneling probability (∼0.242) and the p-type vertical Schottky barrier of about 0.20 eV for the Pt/LH-MoS2 interface were achieved. Compared to other reported BN or graphene tunneling layers, such a BN-graphene LH tunneling layer not only suppressed the charge scattering from the metal electrode to the MoS2 layer and the Fermi level pinning effect, but also reduced the contact resistance between metal electrode and tunneling layer. The underlying mechanisms were revealed to be due to the charge transfer, orbitals and interfacial dipole. This work improves the current understanding of the metal-MoS2 interface and proposes a new way to overcome the current severe contact issues for future nanoelectronic and optoelectronic applications.

Novel secondary metabolites from the endobryophytic fungus Botrysphaeria laricina and their biological activity.

One novel polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid metabolite, laricinin A (1), two new meroterpenoids, tricycloalternarenes X and Y (2 and 3), one new coumarin, 3,4,7-trihydroxy-6-methylcoumarin (4), together with the known ethyl acetylorsellinate (5), diorcinol K (6), and tricycloalternarenes C and D (7 and 8) were obtained from culture of the fungus Botrysphaeria laricina isolated from the moss Rhodobryum umgiganteum. The structures of the new compounds were elucidated based on extensive spectroscopic techniques including HRMS and 1D and 2D NMR measurements. The absolute configuration of compound 1 was determined by ECD calculation and it was the first example of a novel group of PKS-NRPS hybrids possessing an unprecedented methyldihydropyran-isobutylpyrrolidinone skeleton. Compounds 2, 7, and 8 showed significant quinone reductase inducing activity in Hepa 1c1c7 cells.

Novel diterpenoid-type activators of the Keap1/Nrf2/ARE signaling pathway and their regulation of redox homeostasis.

Oxidative stress is involved in the onset and progression of many human diseases. Activators of the Keap1/Nrf2/ARE pathway effectively inhibit the progression of oxidative stress-induced diseases. Herein, a small library of diterpenoids was established by means of phytochemical isolation, and chemical modification on naturally occurring molecules. The diterpenoids were subjected to a NAD(P)H: quinone reductase (QR) assay to evaluate its potential inhibition against oxidative stress. Sixteen diterpenoids were found to be novel potential activators of Nrf2-mediated defensive response. Of which, an isopimarane-type diterpenoid, sphaeropsidin A (SA), was identified as a potent activator of the Keap1/Nrf2/ARE pathway, and displayed approximately 5-folds potency than that of sulforaphane (SF). SA activated Nrf2 and its downstream cytoprotective genes through enhancing the stabilization of Nrf2 in a process involving PI3K, PKC, and PERK, as well as potentially interrupting Nrf2-Keap1 protein-protein interaction. In addition, SA conferred protection against sodium arsenite [As(III)]- and cigarette smoke extract (CSE)-induced redox imbalance and cytotoxicity in human lung epithelial cells, as wells as inhibited metronidazole (MTZ)-induced oxidative insult in Tg (krt4: NTR-hKikGR)cy17 transgenic zebrafish and lipopolysaccharide (LPS)-induced oxidative damage in wild-type AB zebrafish. These results imply that SA is a lead compound for therapeutic agent against oxidative stress-induced diseases, and diterpenoid is a good resource for discovering drug candidates and leads of antioxidant therapy.

Botrysphones A-C and Botrysphins A-F, Triketides and Diterpenoids from the Fungus Botrysphaeria laricina.

Three new triketides, botrysphones A-C (1-3) and six new isopimarane-type diterpenoids, botrysphins A-F (4-9), together with the known triketides sphaeropsidone (10) and chlorosphaeropsidone (11) and diterpenoids sphaeropsidins A and B (12 and 13), were obtained from culture of the fungus Botrysphaeria laricina associated with the moss Rhodobryum umgiganteum. The structures of the new compounds were established on the basis of extensive spectroscopic techniques including HRMS and 1D and 2D NMR data. Compounds 7 and 12 showed significant quinone reductase inducing activity in Hepa 1c1c7 cells.

Pathogen characteristics and its sensitivity against antimicrobial agents in fatal bacterial granuloma after eyelid trauma in vitro.

AIM: To understand the pathogen characteristics and its sensitivity against antimicrobial agents in fatal bacterial granuloma after eyelid trauma (FBGT) in vitro, and to provide laboratory evidence for diagnosis. METHODS: The FBGT pathogens were isolaated and cultured with reformed rabbit-brain anaerobic enriched broth (RRAB), and identified by ATB/API 20A system. The minimum inhibiting concentration (MIC) was determined by anaerobic broth dilution method. RESULTS: A total of 22 strains of pathogen were separated from 21 patients with FBGT and identified as Propionibacterium acnes (PA) by ATB/API 20A system. The MIC of ciprofloxacin for 22 PA strains was 0.0625-0.5mg/L, the MIC of penicillin, ampicillin, ampicillin/sulbactam, cefoperazone, lincomycin, and imipenem/cilastatin were 0.125-0.5mg/L, the MIC of ticarcillin/clavulanic acid was 0.250-1.000 mg/L, and the MIC of metronidazole was 64-256mg/L. The pathogen of FBGT was strictly anaerobic PA, which growed slowly and better in nutritious RRAB broth. All PA were resistant to metronidazole, but susceptive to other routine antimicrobial agents, such as penicillin, ampicillin and lincomycin. CONCLUSION: [corrected] FBGT should not be treated with metronidazole. Clinicians should choose combined use of drugs or operation to treat FBGT according to patients' individual condition and the results of drug sensitivity test.