NADase CD38 is a key determinant of ovarian aging.

The ovary ages earlier than most other tissues, yet the underlying mechanisms remain elusive. Here a comprehensive analysis of transcriptomic landscapes in different organs in young and middle-aged mice revealed that the ovaries showed earlier expression of age-associated genes, identifying increased NADase CD38 expression and decreased NAD+ levels in the ovary of middle-aged mice. Bulk and single-cell RNA sequencing revealed that CD38 deletion mitigated ovarian aging, preserving fertility and follicle reserve in aged mice by countering age-related gene expression changes and intercellular communication alterations. Mechanistically, the earlier onset of inflammation induced higher expression levels of CD38 and decreased NAD+ levels in the ovary, thereby accelerating ovarian aging. Consistently, pharmacological inhibition of CD38 enhanced fertility in middle-aged mice. Our findings revealed the mechanisms underlying the earlier aging of the ovary relative to other organs, providing a potential therapeutic target for ameliorating age-related female infertility.

Melatonin activates mitochondrial unfolded protein response to preserve osteogenic potential of senescent BMSCs via upregulating PDI-6.

Bone marrow stromal cells (BMSCs) possess the capability to differentiate into osteogenic or adipogenic lineages. With aging, BMSCs suffer from mitochondrial dysfunction and undergo senescence, favoring adipogenesis at the expense of osteoblastogenesis. It leads to decreased bone formation and contributes to senile osteoporosis (SOP). In the current study, RNA-seq analysis unveiled that senescent BMSCs from mice exhibited a significant suppression in the expression of the protein disulfide isomerase PDI-6, an important regulator of mitochondrial unfolded protein response (UPRmt) as well as maintenance of mitochondrial homeostasis. Overexpression of PDI-6 in senescent BMSCs partially rescued mitochondrial function and enhanced osteogenic differentiation. In contrast, osteoblastogenesis of BMSCs remarkably deteriorated under the condition of PDI-6 silencing. Furthermore, melatonin, an endocrine hormone, effectively enhanced PDI-6 expression and repaired injured mitochondria, and the effect of melatonin on PDI-6 expression was melatonin receptor dependent. We further identified that PDI-6 was a downstream effector of Wnt/ß-catenin pathway, as the inhibitor of Wnt3A/TCF signaling, Wnt-C59, inhibited PDI-6 expression. Potential ß-catenin-TCF/LEF binding sites on the promoter of PDI-6 gene were also validated by chromatin immunoprecipitation (ChIP) assay. Thus, our study suggests that PDI-6 is a pharmacological target of melatonin for the intervention of age-related osteoporosis via mitigating mitochondrial dysfunction in senescent BMSCs.

Recent advances in sterilization and disinfection technology: A review.

Sterilization and disinfection of pollutants and microorganisms have been extensively studied in order to address the problem of environmental contamination, which is a crucial issue for public health and economics. Various form of hazardous materials/pollutants including microorganisms and harmful gases are released into the environment that enter into the human body either through inhalation, adsorption or ingestion. The human death rate rises due to various respiratory ailments, strokes, lung cancer, and heart disorders related with these pollutants. Hence, it is essential to control the environmental pollution by applying economical and effective sterilization and disinfections techniques to save life. In general, numerous forms of traditional physical and chemical sterilization and disinfection treatments, such as dry and moist heat, radiation, filtration, ethylene oxide, ozone, hydrogen peroxide, etc. are known along with advanced techniques. In this review we summarized both advanced and conventional techniques of sterilization and disinfection along with their uses and mode of action. This review gives the knowledge about the advantages, disadvantages of both the methods comparatively. Despite, the effective solution given by the advanced sterilization and disinfection technology, joint technologies of sterilization and disinfection has proven to be more effective innovation to protect the indoor and outdoor environments.

Ionic liquid exfoliated Ti3C2Tx MXene nanosheets for photoacoustic imaging and synergistic photothermal/chemotherapy of cancer.

Ti3C2Tx MXene is a new type of two-dimensional material with good biocompatibility and a good photothermal effect, and shows great potential in cancer treatment. In this study, few-layer ionic liquid (IL)-Ti3C2Tx MXene nanosheets were synthesized using IL stripping technology, which have high chemical stability, and allow photoacoustic imaging and synergistic photothermal/chemotherapy of cancer. Under 808 nm laser irradiation, the nanosheets have strong absorption in the near-infrared region, and high photothermal conversion efficiency (∼63.91%). Using DOX as a model drug, the IL-Ti3C2Tx MXene@DOX nanosheets exhibited high drug loading capacity and pH-/photosensitivity, which will further promote the drug release of the nanosheets in an acidic tumor microenvironment and under 808 nm laser irradiation. In vitro and in vivo experiments showed that IL-Ti3C2Tx MXene@DOX has good biological safety, allows remarkable photoacoustic imaging, and can effectively kill cancer cells with synergistic photothermal/chemotherapy. Therefore, IL-Ti3C2Tx MXene nanosheets are expected to provide powerful and useful two-dimensional nanoplatforms for various biomedical applications.

2D MXene Nanomaterials for Versatile Biomedical Applications: Current Trends and Future Prospects.

Research on 2D nanomaterials is still in its early stages. Most studies have focused on elucidating the unique properties of the materials, whereas only few reports have described the biomedical applications of 2D nanomaterials. Recently, important questions about the interaction of 2D MXene nanomaterials with biological components have been raised. 2D MXenes are monolayer atomic nanosheets derived from MAX phase ceramics. As a new type of inorganic nanosystems, they are being widely used in biology and biomedicine. This review introduces the latest developments in 2D MXenes for the most advanced biomedical applications, including preparation and surface modification strategies, treatment modes, drug delivery, antibacterial activity, bioimaging, sensing, and biocompatibility. Besides, this review also discusses the current development trends and prospects of 2D inorganic nanosheets for further clinical applications. These emerging 2D inorganic MXenes will play an important role in next-generation cancer treatments.

Redox-Sensitive Hyaluronic Acid Polymer Prodrug Nanoparticles for Enhancing Intracellular Drug Self-Delivery and Targeted Cancer Therapy.

Currently, available nanoscale anticancer drug delivery systems have low targeting and release efficiency, limiting their therapeutic effects. Thus, tumor-targeting nanocarriers for self-assembly of amphiphilic polymer-drug conjugates are urgently needed to improve drug targeting and treatment efficacy. Here, we report the construction of a stable, reduction-sensitive prodrug conjugate based on hyaluronic acid-grafted pH-sensitive doxorubicin (DOX). The amphiphilic prodrug copolymer self-assembled into spherical nanoparticles in aqueous solution and exhibited an average diameter of 150 nm. Prodrug micelles were stable in a normal physiological environment and achieve selective and rapid release under acidic pH and/or high reduction conditions. Cell Counting Kit-8, flow cytometry, and live cell imaging assays showed that the prodrug had high targeting and antitumor activity against CD44 receptors. Moreover, in vivo pharmacokinetics and biodistribution studies showed that the prodrug had a longer circulation time in BALB/c mice and higher accumulation in 4T1 tumors. Interestingly, the prodrug could effectively treat tumors with few side effects. These results showed that the DOX prodrug micelles developed in this study may have great potential in targeted therapy.