Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions.

The complex process of aging leads to a gradual deterioration in the function of cells, tissues, and the entire organism, thereby increasing the risk of disease and death. Nicotinamide N-methyltransferase (NNMT) has attracted attention as a potential target for combating aging and its related pathologies. Studies have shown that NNMT activity increases over time, which is closely associated with the onset and progression of age-related diseases. NNMT uses S-adenosylmethionine (SAM) as a methyl donor to facilitate the methylation of nicotinamide (NAM), converting NAM into S-adenosyl-L-homocysteine (SAH) and methylnicotinamide (MNA). This enzymatic action depletes NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and generates SAH, a precursor of homocysteine (Hcy). The reduction in the NAD+ levels and the increase in the Hcy levels are considered important factors in the aging process and age-related diseases. The efficacy of RNA interference (RNAi) therapies and small-molecule inhibitors targeting NNMT demonstrates the potential of NNMT as a therapeutic target. Despite these advances, the exact mechanisms by which NNMT influences aging and age-related diseases remain unclear, and there is a lack of clinical trials involving NNMT inhibitors and RNAi drugs. Therefore, more in-depth research is needed to elucidate the precise functions of NNMT in aging and promote the development of targeted pharmaceutical interventions. This paper aims to explore the specific role of NNMT in aging, and to evaluate its potential as a therapeutic target.

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome.

Metabolic syndrome (MetS) represents a constellation of metabolic abnormalities, typified by obesity, hypertension, hyperglycemia, and hyperlipidemia. It stems from intricate dysregulations in metabolic pathways governing energy and substrate metabolism. While comprehending the precise etiological mechanisms of MetS remains challenging, evidence underscores the pivotal roles of aberrations in lipid metabolism and insulin resistance (IR) in its pathogenesis. Notably, nicotinamide N-methyltransferase (NNMT) has recently surfaced as a promising therapeutic target for addressing MetS. Single nucleotide variants in the NNMT gene are significantly correlated with disturbances in energy metabolism, obesity, type 2 diabetes (T2D), hyperlipidemia, and hypertension. Elevated NNMT gene expression is notably observed in the liver and white adipose tissue (WAT) of individuals with diabetic mice, obesity, and rats afflicted with MetS. Knockdown of NNMT elicits heightened energy expenditure in adipose and hepatic tissues, mitigates lipid accumulation, and enhances insulin sensitivity. NNMT catalyzes the methylation of nicotinamide (NAM) using S-adenosyl-methionine (SAM) as the donor methyl group, resulting in the formation of S-adenosyl-l-homocysteine (SAH) and methylnicotinamide (MNAM). This enzymatic process results in the depletion of NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and the generation of SAH, a precursor of homocysteine (Hcy). Consequently, this cascade leads to reduced NAD+ levels and elevated Hcy levels, implicating NNMT in the pathogenesis of MetS. Moreover, experimental studies employing RNA interference (RNAi) strategies and small molecule inhibitors targeting NNMT have underscored its potential as a therapeutic target for preventing or treating MetS-related diseases. Nonetheless, the precise mechanistic underpinnings remain elusive, and as of yet, clinical trials focusing on NNMT have not been documented. Therefore, further investigations are warranted to elucidate the intricate roles of NNMT in MetS and to develop targeted therapeutic interventions.

Investigation on the effect of output mirror transmission in WS2-based red-light passively Q-switched Pr:ZBLAN all-fiber lasers.

We report the experimental investigation of visible passively Q-switched Pr3+-doped all-fiber lasers with tungsten disulfide (WS2) saturable absorber, where red-light short-pulse generations from different output mirror transmissions are systemically characterized. The proposed simple and compact all-fiber linear cavity was constructed by a fiber-pigtail-based blue laser-diode pump, a Pr3+-doped fluorozirconate glass active fiber, and the fiber end-facet mirrors. Integrating a free-standing layered WS2 film into the laser cavity initiated the Q-switching operation. Stable microsecond-duration output pulses with kilohertz repetition rates are achieved, corresponding to a few mW/nJ average output power and single-pulse energy. The comparisons on red-light Q-switched output parameters for output transmissions of both ∼40% and ∼80% are performed. This work could provide a useful guideline to manipulate the output performance of visible pulsed all-fiber lasers for various practical applications.

Demonstration of patterned polymer-stabilized cholesteric liquid crystal textures for anti-counterfeiting two-dimensional barcodes.

We evaluated the feasibility of embedding periodically arranged squares with planar and vertical texture into a background with a developable-modulation (DM) type cholesteric liquid crystal (CLC) fingerprint texture by a two-step ultraviolet-induced polymerization method. Checker-patterned optical diffractive elements, which can be seen as a variation of a two-dimensional (2D) barcode, were first realized and the dependence of diffraction behaviors on incident light polarization and applied voltage were investigated. Taking advantage of the natural randomness and uncontrollable variations of a DM-type fingerprint textures, a polymer-stabilized CLC (PSCLC) graphic symbol with a 2D barcode pattern was then implemented with enhanced anti-counterfeiting features that are difficult to falsify or duplicate. The results indicate that the multiplexing of nonuniform DM-type fingerprint gratings, cross-polarized light readout, and unique polarization diffraction characteristics can improve the level of security.

All-fiber passively Q-switched 604 nm praseodymium laser with a Bi2Se3 saturable absorber.

We experimentally demonstrated a simple passively Q-switched praseodymium (Pr3+)-doped all-fiber laser at 604 nm with a Bi2Se3 saturable absorber (SA). A Bi2Se3/polyvinyl alcohol composite film is sandwiched between two ferrules to construct a fiber-compatible Q-switcher. Two fiber end facet mirrors build a compact-linear resonator. The repetition rate of the achieved 604 nm Q-switching pulse can be widely tuned from 86.2 to 187.4 kHz, and the pulse duration can be as narrow as 494 ns. To the best of our knowledge, this is the shortest operation wavelength of a Bi2Se3-based pulsed all-fiber laser at 604 nm.

Immunogenicity of recombinant human zona pellucida-3 peptides expressed in E. coli and efficacy of their antisera to inhibit in vitro human sperm-egg binding / 生理学报

The present study was aimed to analyze the immunogenicity of recombinant human zona pellucida-3 peptides (r-huZP3a(22 approximately 176) and r-huZP3b(177 approximately 348)) expressed in E. coli through immunizing rabbits, and to evaluate the efficacy of their polyclonal antisera against r-huZP3a(22 approximately 176) and r-huZP3b(177 approximately 348) to inhibit in vitro human sperm-egg binding respectively. Male New Zealand rabbits were immunized using r-huZP3a(22 approximately 176) or r-huZP3b(177 approximately 348) as antigen respectively, which was purified through an improved method of preparative gel polyacryulamide gel electrophoresis. The antibody response level of r-huZP3a(22 approximately 176) or r-huZP3b(177 approximately 348) immunogen in rabbits was determined by ELISA using mouse ZP3-5 (amino acid sequence(137 approximately 150) being completely conserved with huZP3(138 approximately 151) sequence) and specific huZP3-14 (amino acid sequence(327 approximately 340)) synthetic peptides as coating antigens respectively. The immunoreactivity and specificity of the anti-r-huZP3a(22 approximately 176) and anti-r-huZP3b(177 approximately 348) antisera with each r-huZP3 peptides, were tested by immunoblot and immunohistochemistry (using native huZP and human ovary section) respectively. A competitive hemizona assay (HZA) was used to evaluate the efficacy of the antisera against r-huZP3a(22 approximately 176) and r-huZP3b(177 approximately 348) to inhibit in vitro human sperm-egg binding. Both r-huZP3 peptides were able to induce higher antibody titers in rabbits. Each antiserum could specifically recognize or bind to each target r-huZP3 peptide expressed in E. coli and native human ZP in vitro. The antisera also inhibited sperm-egg binding in the HZA. These results show that r-huZP3a(22 approximately 176) and r-huZP3b(177 approximately 348) are of strong immunogenicity. They can be used to develop a kit for detecting whether there are autoantibodies to zona pellucida in unexplained infertile women, and their antisera might be useful tools for determining minimal B-cell epitope sequences of several known huZP3 epitope peptides.

Advances in molecular mechanisms of human sperm-egg interaction and infertility / 中华男科学杂志

Human sperm-egg recognition, adhesion and fusion are key steps in the whole reproductive process. Some abnormalities in human gamete interaction have been shown to be due to defects in the sperm, others attributed to defects in the zona pellucida (ZP) and the egg plasma membrane. This paper reviews the molecular basis and molecular mechanisms of human sperm-egg interaction. More and more advances in the studies of these aspects are shown to be of significant value to the diagnosis and treatment of infertility as well as to the development of assisted reproductive techniques.