Mitigating Adverse Effects of Cu-containing Intrauterine Devices Using A Highly Biocompatible Cu-5Fe alloy.

Copper-containing intrauterine devices (Cu-IUD) are adopted by worldwide women for contraception with the advantages of long-term effectiveness, reversibility and affordability. However, adverse effects occur in the initial implantation stage of Cu-IUD in uterine because of the burst release of Cu2+. To minimize the burst release, in this study, we designed a series of Cu-Fe alloys with 0.5 wt%, 1 wt% and 5 wt% Fe and also further produced ultrafine grained (UFG) structure for these alloys via equal-channel angular pressing. The microstructures and properties of the coarse grained (CG) Cu, CG Cu-Fe alloys and UFG Cu-Fe alloys were systematically investigated, including grain structure and phase compositions, metallic ions release behavior, electrochemical corrosion performance, and in vitro cytotoxicity. With careful comparison and selection, we chose the CG Cu-5Fe and UFG Cu-5Fe for in vivo tests using rat model, including tissue biocompatibility, in vivo corrosion behavior, and contraceptive effectiveness. Moreover, the corrosion mechanism of the Cu-5Fe alloy and its improved biocompatibility was discussed. Both CG and UFG Cu-5Fe alloys exhibited dramatic suppression of Cu2+ release in simulated uterine fluid for the long-term immersion process. The in vivo tissue compatibility was significantly improved with both CG and UFG Cu-5Fe alloys implanted in the rats' uterine while the high contraceptive efficacy was well maintained. Due to the superior biocompatibility, the CG and UFG Cu-5Fe alloys can be the promising candidate material for Cu-IUD. STATEMENT OF SIGNIFICANCE: A highly biocompatible Cu-Fe alloy was designed and fabricated for Cu-containing intrauterine devices (Cu-IUD). With 5wt% Fe, the burst release of Cu2+ is inhibited due to the formed galvanic cell of Cu and Fe, resulting in earlier release of Fe3+. As Fe is the most abundant essential trace element of human body, it can mitigate the toxic effects of Cu2+, thus significantly improving both in vitro cell compatibility and in vivo tissue compatibility. More importantly, the Cu-5Fe alloy exhibits 100% contraceptive efficiency as the CG Cu, but with greatly reduced adverse effects to the uterus tissues. An advanced Cu-IUD can be developed using Cu-Fe alloys.

High-Voltage Power Supply for Four-Quadrant Dielectric Elastomer Actuators.

Dielectric elastomer actuators (DEAs) are emerging as promising candidates for various applications in robotics and optical devices due to their lightweight, miniaturization potential, high energy density, simple structure, and low power consumption. However, their effective actuation always demands sophisticated high-voltage driving circuits that are compact and responsive. DEAs need to be capable of generating intricate high-voltage waveforms or simultaneously controlling multiple quadrants with distinct high-voltage levels. This paper proposes a high-voltage power supply for DEAs, featuring a four-quadrant high-voltage driving circuit. The circuit is capable of independently generating high-voltage signals ranging from 100 V to 6000 V and producing arbitrary waveforms with adjustable frequencies. The independent operation of the quadrants without crosstalk showcases the system's integration and potential for cross-disciplinary applications.

Molecular insights into the catabolism of dibutyl phthalate in Pseudomonas aeruginosa PS1 based on biochemical and multi-omics approaches.

A comprehensive understanding of the molecular mechanisms underlying microbial catabolism of dibutyl phthalate (DBP) is still lacking. Here, we newly isolated a bacterial strain identified as Pseudomonas aeruginosa PS1 with high efficiency of DBP degradation. The degradation ratios of DBP at 100-1000 mg/L by this strain reached 80-99 % within 72 h without a lag phase. A rare DBP-degradation pathway containing two monobutyl phthalate-catabolism steps was proposed based on intermediates identified by HPLC-TOF-MS/MS. In combination with genomic and transcriptomic analyses, we identified 66 key genes involved in DBP biodegradation and revealed the genetic basis for a new complete catabolic pathway from DBP to Succinyl-CoA or Acetyl-CoA in the genus Pseudomonas for the first time. Notably, we found that a series of homologous genes in Pht and Pca clusters were simultaneously activated under DBP exposure and some key intermediate degradation related gene clusters including Pht, Pca, Xyl, Ben, and Cat exhibited a favorable coexisting pattern, which contributed the high-efficient DBP degradation ability and strong adaptability to this strain. Overall, these results broaden the knowledge of the catabolic diversity of DBP in microorganisms and enhance our understanding of the molecular mechanism underlying DBP biodegradation.

Combination of disulfiram and Copper-Cysteamine nanoparticles induces mitochondria damage and promotes apoptosis in endometrial cancer.

Endometrial cancer (EC) stands as one of the most prevalent gynecological malignancies affecting women, with its incidence and disease-related mortality steadily on the rise. Disulfiram (DSF), an FDA-approved medication primarily used for treating alcohol addiction, has exhibited promising anti-tumor properties. Studies have revealed DSF's capacity for enhanced anti-tumor activity, particularly when combined with copper. The novel Copper-Cysteamine (CuCy) compound, Cu3Cl(SR)2 (R[bond, double bond]CH2CH2NH2), showcases photodynamic effects and demonstrates significant anti-tumor potential under various conditions, including exposure to ultraviolet light, X-ray, microwave, and ultrasound. This study delves into exploring the synergistic anti-tumor effects and underlying mechanisms by utilizing copper-cysteamine in conjunction with DSF against endometrial cancer. The investigation involved comprehensive analyses encompassing in vitro experiments utilizing Ishikawa cells, in vivo studies, and transcriptomic analyses. Remarkably, the combined administration of both compounds at a low dose of 0.5 µM exhibited pronounced efficacy in impeding tumor growth, inhibiting blood vessel formation, and stimulating cell apoptosis. Notably, experiments involving transplanted tumors in nude mice vividly demonstrated the significant in vivo anti-tumor effects of this combination treatment. Detailed examination through transmission electron microscopy unveiled compelling evidence of mitochondrial damage, cellular swelling, and rupture, indicative of apoptotic changes in morphology due to the combined treatment. Moreover, transcriptomic analysis unveiled substantial downregulation of mitochondrial-related genes at the molecular level, coupled with a significant hindrance in the DNA repair pathway. These findings strongly suggest that the combined application of CuCy and DSF induces mitochondrial impairment in Ishikawa cells, thereby fostering apoptosis and ultimately yielding potent anti-tumor effects.

Nanostrategy of Targeting at Embryonic Trophoblast Cells Using CuO Nanoparticles for Female Contraception.

Effective contraceptives have been comprehensively adopted by women to prevent the negative consequences of unintended pregnancy for women, families, and societies. With great contributions of traditional hormonal drugs and intrauterine devices (IUDs) to effective female contraception by inhibiting ovulation and deactivating sperm, their long-standing side effects on hormonal homeostasis and reproductive organs for females remain concerns. Herein, we proposed a nanostrategy for female contraceptives, inducing embryonic trophoblast cell death using nanoparticles to prevent embryo implantation. Cupric oxide nanoparticles (CuO NPs) were adopted in this work to verify the feasibility of the nanostrategy and its contraceptive efficacy. We carried out the in vitro assessment on the interaction of CuO NPs with trophoblast cells using the HTR8/SVneo cell line. The results showed that the CuO NPs were able to be preferably uptaken into cells and induced cell damage via a variety of pathways including oxidative stress, mitochondrial damage, DNA damage, and cell cycle arrest to induce cell death of apoptosis, ferroptosis, and cuproptosis. Moreover, the key regulatory processes and the key genes for cell damage and cell death caused by CuO NPs were revealed by RNA-Seq. We also conducted in vivo experiments using a rat model to examine the contraceptive efficacy of both the bare CuO NPs and the CuO/thermosensitive hydrogel nanocomposite. The results demonstrated that the CuO NPs were highly effective for contraception. There was no sign of disrupting the homeostasis of copper and hormone, or causing inflammation and organ damage in vivo. In all, this nanostrategy exhibited huge potential for contraceptive development with high biosafety, efficacy, clinical translation, nonhormonal style, and on-demand for women.

Nanomaterials Solutions for Contraception: Concerns, Advances, and Prospects.

Preventing unintentional pregnancy is one of the goals of a global public health policy to minimize effects on individuals, families, and society. Various contraceptive formulations with high effectiveness and acceptance, including intrauterine devices, hormonal patches for females, and condoms and vasectomy for males, have been developed and adopted over the last decades. However, distinct breakthroughs of contraceptive techniques have not yet been achieved, while the associated long-term adverse effects are insurmountable, such as endocrine system disorder along with hormone administration, invasive ligation, and slowly restored fertility after removal of intrauterine devices. Spurred by developments of nanomaterials and bionanotechnologies, advanced contraceptives could be fulfilled via nanomaterial solutions with much safer and more controllable and effective approaches to meet various and specific needs for women and men at different reproductive stages. Nanomedicine techniques have been extended to develop contraceptive methods, such as the targeted drug delivery and controlled release of hormone using nanocarriers for females and physical stimulation assisted vasectomy using functional nanomaterials via photothermal treatment or magnetic hyperthermia for males. Nanomaterial solutions for advanced contraceptives offer significantly improved biosafety, noninvasive administration, and controllable reversibility. This review summarizes the nanomaterial solutions to female and male contraceptives including the working mechanisms, clinical concerns, and their merits and demerits. This work also reviewed the nanomaterials that have been adopted in contraceptive applications. In addition, we further discuss safety considerations and future perspectives of nanomaterials in nanostrategy development for next-generation contraceptives. We expect that nanomaterials would potentially replace conventional materials for contraception in the near future.