Cutting-edge biotechnological advancement in islet delivery using pancreatic and cellular approaches.

There are approximately 1 billion prediabetic people worldwide, and the global cost for diabetes mellitus (DM) is estimated to be $825 billion. In regard to Type 1 DM, transplanting a whole pancreas or its islets has gained the attention of researchers in the last few decades. Recent studies showed that islet transplantation (ILT) containing insulin-producing β cells is the most notable advancement cure for Type 1 DM. However, this procedure has been hindered by shortage and lack of sufficient islet donors and the need for long-term immunosuppression of any potential graft rejection. The strategy of encapsulation may avoid the rejection of stem-cell-derived allogeneic islets or xenogeneic islets. This review article describes various biotechnology features in encapsulation-of-islet-cell therapy for humans, including the use of bile acids

Förster Resonance Energy Transfer Sensitized Singlet Fission in BODIPY-Pentacene Dimer Conjugates

In the present work, the energy donor 4,4-difluoro-4-bora-3a,4a-diaza-sindacene (BODIPY) is used for the first time in combination with a pentacene dimer (Pnc2) to provide the conjugate BODIPYPnc2 that features absorption throughout a large part of the solar spectrum. Upon photoexcitation, the singlet excited state energy of BODIPY is transferred to the pentacene dimer via intramolecular Förster resonance energy transfer (FRET). Subsequently, the pentacene dimer undergoes intramolecular singlet fission. In this process, a singlet correlated triplet pair is generated from the first singlet excited state via coupling to an intermediate state. The results show that solvent polarity has an influence on the system, with the largest FRET rate (i.e., 7.46 × 1011 s−1) being obtained in the most polar solvent (namely, benzonitrile) along with the largest triplet quantum yield (i.e., 207 ± 20%)A.-S.W., G.L., and I.P. contributed equally to this work. D.M.G. thanks the financial support from ″the German Research Foundation (DFG) via SFB 953 “Synthetic Carbon Allotropes” and “Solar Technologies go Hybrid (SolTech)” Initiative of the Bavarian Ministry for Science. T.T. acknowledges financial support from MICINN (PID2020-116490GB-I00 and TED2021-131255B-C43), the Comunidad de Madrid and the Spanish State through the Recovery, Transformation and Resilience Plan [“Materiales Disruptivos Bidimensionales (2D)” (MAD2D-CM) (UAM1)-MRR Materiales Avanzados], and the European Union through the Next Generation EU funds. IMDEA Nanociencia acknowledges support from the “Severo Ochoa” Programme for Centres of Excellence in R&D (MINECO, Grant SEV2016-0686). R.R.T. acknowledges funding from the Natural Sciences and Engineering Research Council of Canada (NSERC, grant no. RGPIN-2017-05052) and the Canada Foundation for Innovation (CFI

Low Circulating IGF-I Bioactivity in Elderly Men is associated with Increased Mortality

Context: Low IGF-I signaling activity prolongs lifespan in certain animal models, but the precise role of IGF-I in human survival remains controversial. The IGF-I kinase receptor activation assay (IGF-I KIRA) is a novel method for measuring IGF-I bioactivity in human serum. We speculated that determination of circulating IGF-I bioactivity is more informative than levels of immunoreactive IGFI. Objective: To study IGF-I bioactivity in relation to human survival. Design: Prospective observational study. Setting: A clinical research center at a university hospital. Study participants: 376 healthy elderly men (aged 73 to 94 years). Main outcome Measures: IGF-I bioactivity was determined by the IGF-I KIRA. Total and free IGF-I were determined by IGF-I immunoassays. Mortality was registered during follow-up (mean 82 months). Results: During the follow-up period of 8.6 years 170 men (45%) died. Survival of subjects in the highest quartile of IGF-I bioactivity was significantly better than in the lowest quartile, both in the total study group (HR = 1.8, (95% CI: 1.2 − 2.8, p = 0.01) as well as in subgroups having a medical history of cardiovascular disease (HR = 2.4 (95% CI: 1.3 − 4.3, p = 0.003) or a high inflammatory risk profile (HR = 2.3 (95% CI: 1.2 − 4.5, p = 0.01). Significant relationships were not observed for total or free IGF-I. Conclusion: Our study suggests that a relatively high circulating IGF-I bioactivity in elderly men is associated with extended survival and with reduced cardiovascular risk

Characterization of the Interaction and Cross-Regulation of Three Mycobacterium tuberculosis RelBE Modules

RelBE represents a typical bacterial toxin-antitoxin (TA) system. Mycobacterium tuberculosis H37Rv, the pathogen responsible for human tuberculosis, contains three RelBE-like modules, RelBE, RelFG, and RelJK, which are at least partly expressed in human macrophages during infection. RelBE modules appear to be autoregulated in an atypical manner compared to other TA systems; however, the molecular mechanisms and potential interactions between different RelBE modules remain to be elucidated. In the present study, we characterized the interaction and cross-regulation of these Rel toxin-antitoxin modules from this unique pathogen. The physical interactions between the three pairs of RelBE proteins were confirmed and the DNA-binding domain recognized by three RelBE-like pairs and domain structure characteristics were described. The three RelE-like proteins physically interacted with the same RelB-like protein, and could conditionally regulate its binding with promoter DNA. The RelBE-like modules exerted complex cross-regulation effects on mycobacterial growth. The relB antitoxin gene could replace relF in cross-neutralizing the relG toxin gene. Conversely, relF enhanced the toxicity of the relE toxin gene, while relB increased the toxicity of relK. This is the first report of interactions between different pairs of RelBE modules of M. tuberculosis

Dental and prosthodontic status of an over 40 year-old population in Shandong Province, China

Contains fulltext : 97791.pdf (postprint version ) (Open Access)BACKGROUND: This study aims to (1) describe the dental status using DMFT for the whole dentition and the anterior, premolar and molar regions; (2) determine associations of demographic variables and socio-economic status (SES) with DMFT and tooth replacement; (3) analyze to what extent the goal as proposed by the WHO -'the retention of not less than 20 teeth throughout life' is achieved. METHODS: DMFT and tooth replacement data of 1588 subjects over 40 years from urban and rural sites in Qingdao (Shandong Province, China) were collected. Relative D, M, and F scores per dental region were calculated and compared by paired T-tests. Multivariable logistic regression was used to determine relationships with age, gender, place of residence, and SES. RESULTS: Mean numbers of D and F were low (1.36 respectively 0.27) at all ages. Molars had highest chance for D and M. For the molar region every additional year of age gave significantly lower chance for D and higher chance for M (OR: 0.98 and 1.02 respectively; both p </= 0.01). Mean number of M was associated with age (approximately 1.5 in each jaw at 40 years and 6 at 80 years). Females had higher chance for D (OR: 1.34; p </= 0.05) and F (OR: 1.69; p </= 0.01), and lower chance for M (OR: 0.60; p </= 0.01). Urban and rural subjects had similar chance for D; urban subjects had approximately 5 times more chance for F (p </= 0.01). SES had no relationship with D and M, however SES low was associated with F (OR: 0.45; p </= 0.01). Replacements were significantly associated with age (all dental regions except anterior region), gender (all dental regions), place of residence (whole dentition and molar region), and SES (whole dentition and premolar and molar regions). CONCLUSIONS: The majority of subjects presented a reduced dentition. Molars were most frequently affected by D and M. D, M, F and replaced teeth were associated with the background variables, however differently for different dental regions. Above the age of 70 years, only 64% of the subjects presented 'not less than 20 natural teeth'

Smoking cessation and lung cancer risk in an Asian population: Findings from the Singapore Chinese Health Study

10.1038/sj.bjc.6605782British Journal of Cancer10371093-1096BJCA

Template‐Directed Synthesis of Strained meso‐meso‐Linked Porphyrin Nanorings

Strained macrocycles display interesting properties, such as conformational rigidity, often resulting in enhance π‐conjugation or enhanced affinity for non‐covalent guest binding, yet they can be difficult to synthesize. Here we use computational modeling to design a template to direct the formation of an 18‐porphyrin nanoring with direct meso‐meso bonds between the porphyrin units. Coupling of a linear 18‐porphyrin oligomer in the presence of this template gives the target nanoring, together with an unexpected 36‐porphyrin ring by‐product. Scanning tunneling microscopy (STM) revealed the elliptical conformations and flexibility of these nanorings on a Au(111) surface

Molecular and Chemical Characterization of the Biosynthesis of the 6-MSA-Derived Meroterpenoid Yanuthone D in Aspergillus niger.

SummarySecondary metabolites in filamentous fungi constitute a rich source of bioactive molecules. We have deduced the genetic and biosynthetic pathway of the antibiotic yanuthone D from Aspergillus niger. Our analyses show that yanuthone D is a meroterpenoid derived from the polyketide 6-methylsalicylic acid (6-MSA). Yanuthone D formation depends on a cluster composed of ten genes including yanA and yanI, which encode a 6-MSA polyketide synthase and a previously undescribed O-mevalon transferase, respectively. In addition, several branching points in the pathway were discovered, revealing five yanuthones (F, G, H, I, and J). Furthermore, we have identified another compound (yanuthone X1) that defines a class of yanuthones that depend on several enzymatic activities encoded by genes in the yan cluster but that are not derived from 6-MSA