Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner.

Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD + can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD + precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known. Here we investigate the effect of long-term administration of NMN on the health, cancer burden, frailty and lifespan of male and female mice. Without increasing tumor counts or severity in any tissue, NMN treatment of males and females increased activity, maintained more youthful gene expression patterns, and reduced overall frailty. Reduced frailty with NMN treatment was associated with increases in levels of Anerotruncus colihominis, a gut bacterium associated with lower inflammation in mice and increased longevity in humans. NMN slowed the accumulation of adipose tissue later in life and improved metabolic health in male but not female mice, while in females but not males, NMN increased median lifespan by 8.5%, possible due to sex-specific effects of NMN on NAD + metabolism. Together, these data show that chronic NMN treatment delays frailty, alters the microbiome, improves male metabolic health, and increases female mouse lifespan, without increasing cancer burden. These results highlight the potential of NAD + boosters for treating age-related conditions and the importance of using both sexes for interventional lifespan studies.

Rational designing NiVO3@CoNi-MOF heterostructures on activated carbon cloth for high-performance asymmetric supercapacitors and oxygen evolution reaction.

Binder-free self-supported carbon cloth electrode provides novel strategies for the preparation of MOFs, effectively improving the conductivity and promoting charge transfer. Combining MOFs with vanadate to form a unique heterogeneous structure provides a large specific surface area and more active sites, further enhancing the kinetics of MOFs. Herein, a self-supported carbon cloth electrode is prepared by in-situ growth of CoNi-MOFs on activated carbon cloth (AC) and coating with NiVO3. The heterostructure increases the specific surface area and exposes more active sites to promote the adsorption and diffusion of ions, thus enhancing the kinetic activity and optimizing charge storage behavior. As expected, the NiVO3@CoNi-MOF/AC exhibits a specific capacitance of up to 19.20 F/cm2 at 1 mA/cm2. The asymmetric supercapacitors (ASCs) assembled by NiVO3@CoNi-MOF/AC and annealed activated carbon cloth achieve an energy density of 1.27 mWh/cm2 at a power density of 4 mW/cm2 and have a capacitance retention of 96.43 % after 10,000 cycles. In addition, the NiVO3@CoNi-MOF/AC as electrocatalyst has an overpotential of 370 mV at 10 mA/cm2 and a Tafel slope of 208 mV dec-1, demonstrating remarkable electrocatalytic oxygen evolution reaction performance. These unique heterostructures endow the electrode with more electrochemical selectivity and provide new key insights for designing multifunctional materials.

TIME-seq reduces time and cost of DNA methylation measurement for epigenetic clock construction.

Epigenetic 'clocks' based on DNA methylation have emerged as the most robust and widely used aging biomarkers, but conventional methods for applying them are expensive and laborious. Here we develop tagmentation-based indexing for methylation sequencing (TIME-seq), a highly multiplexed and scalable method for low-cost epigenetic clocks. Using TIME-seq, we applied multi-tissue and tissue-specific epigenetic clocks in over 1,800 mouse DNA samples from eight tissue and cell types. We show that TIME-seq clocks are accurate and robust, enriched for polycomb repressive complex 2-regulated loci, and benchmark favorably against conventional methods despite being up to 100-fold less expensive. Using dietary treatments and gene therapy, we find that TIME-seq clocks reflect diverse interventions in multiple tissues. Finally, we develop an economical human blood clock (R > 0.96, median error = 3.39 years) in 1,056 demographically representative individuals. These methods will enable more efficient epigenetic clock measurement in larger-scale human and animal studies.

Chemically induced reprogramming to reverse cellular aging.

A hallmark of eukaryotic aging is a loss of epigenetic information, a process that can be reversed. We have previously shown that the ectopic induction of the Yamanaka factors OCT4, SOX2, and KLF4 (OSK) in mammals can restore youthful DNA methylation patterns, transcript profiles, and tissue function, without erasing cellular identity, a process that requires active DNA demethylation. To screen for molecules that reverse cellular aging and rejuvenate human cells without altering the genome, we developed high-throughput cell-based assays that distinguish young from old and senescent cells, including transcription-based aging clocks and a real-time nucleocytoplasmic compartmentalization (NCC) assay. We identify six chemical cocktails, which, in less than a week and without compromising cellular identity, restore a youthful genome-wide transcript profile and reverse transcriptomic age. Thus, rejuvenation by age reversal can be achieved, not only by genetic, but also chemical means.

A bacterial pan-genome makes gene essentiality strain-dependent and evolvable.

Many bacterial species are represented by a pan-genome, whose genetic repertoire far outstrips that of any single bacterial genome. Here we investigate how a bacterial pan-genome might influence gene essentiality and whether essential genes that are initially critical for the survival of an organism can evolve to become non-essential. By using Transposon insertion sequencing (Tn-seq), whole-genome sequencing and RNA-seq on a set of 36 clinical Streptococcus pneumoniae strains representative of >68% of the species' pan-genome, we identify a species-wide 'essentialome' that can be subdivided into universal, core strain-specific and accessory essential genes. By employing 'forced-evolution experiments', we show that specific genetic changes allow bacteria to bypass essentiality. Moreover, by untangling several genetic mechanisms, we show that gene essentiality can be highly influenced by and/or be dependent on: (1) the composition of the accessory genome, (2) the accumulation of toxic intermediates, (3) functional redundancy, (4) efficient recycling of critical metabolites and (5) pathway rewiring. While this functional characterization underscores the evolvability potential of many essential genes, we also show that genes with differential essentiality remain important antimicrobial drug target candidates, as their inactivation almost always has a severe fitness cost in vivo.

CTLA-4 polymorphisms and predisposition to digestive system malignancies: a meta-analysis of 31 published studies.

BACKGROUND: The results of genetic association studies regarding cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) polymorphisms and digestive system malignancies were controversial. The authors designed this meta-analysis to more precisely estimate relationships between CTLA-4 polymorphisms and digestive system malignancies by pooling the results of related studies. METHODS: The authors searched PubMed, Embase, Web of Science, and CNKI for eligible studies. Thirty-one eligible studies were pooled analyzed in this meta-analysis. RESULTS: The pooled meta-analysis results showed that genetic distributions of rs231775, rs4553808, and rs733618 polymorphisms among patients with digestive system malignancies and controls differed significantly. Moreover, genotypic distribution differences were also observed for rs231775 polymorphism among patients with colorectal cancer/pancreatic cancer and controls, for rs4553808 and rs5742909 polymorphisms among patients with gastric cancer and controls, for rs3087243 polymorphism among patients with liver cancer and controls, and for rs733618 polymorphism among patients with colorectal cancer and controls in pooled meta-analyses. CONCLUSIONS: This meta-analysis suggested that rs231775 polymorphism was associated with predisposition to colorectal cancer and pancreatic cancer, rs4553808 and rs5742909 polymorphisms were associated with predisposition to gastric cancer, rs3087243 polymorphism was associated with predisposition to liver cancer, and rs733618 polymorphism was associated with predisposition to colorectal cancer.

In situ growth of MnO@Na2Ti6O13 heterojunction nanowires for high performance supercapacitors.

One-dimensional tunnel and layer frame crystal structure materials are extremely attractive for energy storage in electrode materials. The energy storage properties of the electrode materials depend on their conductivity. Furthermore, the conductivity of electrode materials can be tailored through combination or doping with other materials, which transforms their properties from semiconductor to semimetallic or metallic and allow them to show unequaled performance for storage devices. In this work, heterostructures of manganese oxide (MnO) and modified sodium titanate (Na2Ti6O13) (MnO@Na2Ti6O13) nanowires are attained by the in situ thermal decomposition method. The heterojunction between MnO and Na2Ti6O13 allows the semiconductor properties of pure Na2Ti6O13 to show remarkable metallic behavior for improving the electrochemical performance. The capacitance of MnO@Na2Ti6O13 heterojunction nanowires can reach 272.3 F g-1, a power intensity of 250 W kg-1 at the energy density of 37.83 Wh kg-1 and retain 5000 W kg-1 at 6.67 Wh kg-1 as well. The energy storage mechanism of the MnO@Na2Ti6O13 heterostructure is studied by density functional theory. All of the results show that the MnO@Na2Ti6O13 heterostructure material has the potential to be an excellent supercapacitor material in the future.

Direct growth of CuCo2S4 nanosheets on carbon fiber textile with enhanced electrochemical pseudocapacitive properties and electrocatalytic properties towards glucose oxidation.

Flexible and wearable electronic devices with excellent performance have been desired for making the next generation of electronic products. Herein, the synthesis of CuCo2S4 nanosheets on flexible carbon fiber textile (CFT) by a facile one-step and scalable hydrothermal procedure is reported, which is free from the sulphurization process used in the conventional synthesis of mixed metal sulphospinels. The as-prepared CuCo2S4 nanostructures on CFT can provide rich reaction sites and short ion diffusion paths. The CuCo2S4 nanosheets are employed as the free-standing electrodes for two different applications: high-performance supercapacitors and non-enzymatic glucose sensors. When employed as a flexible electrode material for supercapacitors, the electrode presents ultrahigh performance in energy storage with a specific capacitance of 3321.6 F g-1 at 5 A g-1, which is attributed to the suitable mass loading and special morphology of the as-prepared nanosheets. Remarkably, a specific capacitance of 2931.4 F g-1 is still retained at the high current density of 30 A g-1, suggesting its excellent rate capability. The specific capacitance retains 87.1% after 3000 cycles, reflecting excellent cycling performance. For real applications, a flexible symmetric supercapacitor is assembled based on CuCo2S4 nanosheets, which achieves a high energy density of 64.6 W h kg-1 at 499.7 W kg-1 and a maximum power density of 2081.5 W kg-1 at 45.1 W h kg-1. Besides serving as a free-standing electrode for non-enzymatic glucose sensors, CuCo2S4 nanosheets have remarkable electrocatalytic activity towards glucose oxidation with a high sensitivity of 3852.7 µA mM-1 cm-2 and an extraordinary linear range up to 3.67 mM. The experimental results suggest that CuCo2S4 nanosheets are more suitable for non-enzymatic glucose sensors than the related single/binary transition metal oxides/sulfides. Such a superior performance demonstrates that CuCo2S4 nanosheets hold great potential for use as flexible multifunctional electronic devices including supercapacitors and non-enzymatic glucose sensors.

Use of a Holmium laser to treat a forgotten double-J stent with whole stent encrustations: a case report.

Short-term placement of double-J (D-J) ureteral stents after endourologic procedures and some open urological surgery is common. It is rare for a patient to forget about the indwelling D-J ureteral stent, and the major complications associated with that include infection, stone encrustation and multifractured stent. We report a case of a forgotten D-J ureteral stent, which had been placed 24 months previously during ureterorenoscopic lithotripsy, in a 62-year-old man who presented with flank soreness and recurrent urinary tract infection. Radiography of the kidney, ureter and bladder, and computed tomography demonstrated stone encrustation over the whole D-J stent. Cystolithotripsy and ureterorenoscopic lithotripsy with a Holmium laser were performed to remove the D-J. We believe that this is the first case of successful removal of an intact, encrusted stent in one procedure by endoscopic manipulation.