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1.
Reproduction ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39405070

RESUMEN

With an increase in the mean age at parturition worldwide, female reproductive aging has become a key health problem. Advanced maternal age is reflected by decreased oocyte quality; however, the molecular mechanisms of oocyte aging are uncharacterized. O-linked N-acetylglucosamine (O-GlcNAc), a dynamic posttranslational modification, plays a critical role in the development of many age-related diseases, yet it remains unclear whether and how O-GlcNAc participates in oocyte aging. Here, we found that global O-GlcNAc was elevated in normal biological aging mice oocytes (32-34 weeks) which were characterized by meiotic maturation failure and impaired mitochondrial function. Specifically, O-GlcNAc targeted the mitochondrial fission protein dynamic-related protein 1 (DRP1) to meditate mitochondrial distribution in the process of aging. Using the O-GlcNAcase (OGA) pharmacological inhibitor Thiamet-G and OGA knockdown (OGA-KD) to mimic the age-related high O-GlcNAc in young oocytes from 6-8 week-old mice mimicked the phenotype of oocyte aging. Moreover, reducing O-GlcNAc levels in aging oocytes restored spindle organization to improve oocyte quality. Our results demonstrate that O-GlcNAc is a key regulator of meiotic maturation that participates in the progression of oocyte aging.

3.
Adv Mater ; : e2413303, 2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39449497

RESUMEN

The composite gel electrolyte (CGE), which combines the advantages of inorganic solid-state electrolytes and solid polymer electrolytes, is regarded as the ultimate candidate for constructing batteries with high safety and superior electrode-electrolyte interface contact. However, the ubiquitous agglomeration of nanofillers results in low filler utilization, which seriously reduces structural uniformity and ion transport efficiency, thus restricting the development of consistent and durable batteries. Herein, a solution-processable method to in situ construct CGE with high filler utilization is introduced. The homogeneous metal-organic framework fillers contribute to uniform ionic and electronic filed distribution, realizing a stable electrode-electrolyte interface. Consequently, the CGE with high filler utilization achieves an ultra-long lifespan of 10 000 cycles with a capacity retention of 80.2%. This work provides guidance for constructing high-performance CGEs in electrochemical energy-storage devices.

4.
Nat Commun ; 15(1): 6670, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107311

RESUMEN

Thermal management emerges as a grand challenge of next-generation electronics. Efforts to develop compact, solid-state cooling devices have led to the exploration of the electrocaloric effect of ferroelectric polymers. Despite recent advances, the applications of electrocaloric polymers on electronics operating at elevated temperatures remain essentially unexplored. Here, we report that the ferroelectric polymer composite composed of highly-polarized barium strontium titanate nanofibers and electron-accepting [6,6] phenyl-C61-butyric acid methyl ester retains fast electrocaloric responses and stable cyclability at elevated temperatures. We demonstrate the effectiveness of electrocaloric cooling in a polymer composite for a pyroelectric energy harvesting device. The device utilizes a simulated central processing unit (CPU) as the heat source. Our results show that the device remains operational even when the CPU is overheated. Furthermore, we show that the composite functions simultaneously as a pyroelectric energy converter to harvest thermal energy from an overheated chip into electricity in the electrocaloric process. This work suggests a distinct approach for overheating protection and recycling waste heat of microelectronics.

5.
Lipids Health Dis ; 23(1): 180, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862993

RESUMEN

BACKGROUND: The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. METHODS: Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. RESULTS: A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. CONCLUSIONS: This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.


Asunto(s)
Autofagia , Barrera Hematotesticular , Busulfano , Caprilatos , Estrés Oxidativo , Células de Sertoli , Espermatogénesis , Masculino , Animales , Barrera Hematotesticular/efectos de los fármacos , Barrera Hematotesticular/metabolismo , Busulfano/efectos adversos , Caprilatos/farmacología , Estrés Oxidativo/efectos de los fármacos , Ratones , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Humanos , Espermatogénesis/efectos de los fármacos , Autofagia/efectos de los fármacos , Infertilidad Masculina/tratamiento farmacológico , Infertilidad Masculina/inducido químicamente , Infertilidad Masculina/patología , Testículo/efectos de los fármacos , Testículo/patología , Testículo/metabolismo , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Adulto
6.
Cell Prolif ; 57(2): e13551, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37743695

RESUMEN

Busulfan is an antineoplastic, which is always accompanied with the abnormal of spermatogonia self-renewal and differentiation. It has been demonstrated that the omega-3 polyunsaturated fatty acids (PUFAs) benefits mature spermatozoa. However, whether omega-3 can protect endogenous spermatogonia and the detailed mechanisms are still unclear. Evaluate of spermatogenesis function (in vivo) were examined by histopathological analysis, immunofluorescence staining, and western blotting. The levels of lipid metabolites in testicular tissue were determined via liquid chromatography. We investigated the effect of lipid metabolites on Sertoli cells provided paracrine factors to regulate spermatogonia proliferation and differentiation using co-culture system. In our study, we showed that omega-3 PUFAs significantly improved the process of sperm production and elevated the quantity of both undifferentiated Lin28+ spermatogonia and differentiated c-kit+ spermatogonia in a mouse model where spermatogenic function was disrupted by busulfan. Mass spectrometry revealed an increase in the levels of several omega-3 metabolites in the testes of mice fed with omega-3 PUFAs. The eicosapentaenoic acid metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) up-regulated bone morphogenic protein 4 (BMP4) expression through GPR120-ERK1/2 pathway activation in Sertoli cells and restored spermatogonia proliferation and differentiation. Our study provides evidence that omega-3 PUFAs metabolite 12-HEPE effectively protects spermatogonia and reveals that GPR120 might be a tractable pharmacological target for fertility in men received chemotherapy or severe spermatogenesis dysfunction.


Asunto(s)
Busulfano , Semen , Humanos , Masculino , Ratones , Animales , Busulfano/farmacología , Busulfano/metabolismo , Espermatogénesis/fisiología , Espermatogonias , Espermatozoides , Testículo/metabolismo
7.
Science ; 382(6676): 1291-1296, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38096305

RESUMEN

The human body must stay within a certain temperature range for comfort and safety. However, challenges for thermoregulatory clothing exist for harsh application scenarios, such as full day/night cycles, frigid polar regions, and space travel. We developed a flexible and sustainable personal thermoregulatory clothing system by integrating a flexible organic photovoltaic (OPV) module to directly acquire energy from sunlight and bidirectional electrocaloric (EC) devices. The flexible OPV-EC thermoregulatory clothing (OETC) can extend the human thermal comfort zone from 22°-28°C to 12.5°-37.6°C with a fast thermoregulation rate. The low energy consumption and high efficiency of the EC device allows for 24 hours of controllable and dual-mode thermoregulation with 12 hours of sunlight energy input. This self-powered wearable thermoregulatory platform has a simple structure, compact design, high efficiency, and strong self-adaptability with sunlight as the sole energy source.

8.
Nano Lett ; 23(23): 11272-11279, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38038230

RESUMEN

Thermogalvanic hydrogels have been quickly developed and are widely used in thermal energy harvesting. However, the freezing behaviors of thermogalvanic hydrogels at subzero temperatures greatly limit their practical applications. Herein, we design an antifreezing thermogalvanic hydrogel based on [Fe(CN)6]3-/4- ions for thermoelectric power generation in ultralow temperature environments. The antifreezing thermogalvanic hydrogels show excellent flexibility at -80 °C owing to the hydrogen bonding between ethylene glycol and water molecules. Even after 500 cyclic tensile strains, the thermogalvanic hydrogels can still maintain excellent mechanical stability, and the Seebeck coefficient is as high as 1.43 mV/K, corresponding to a large retention rate of ∼95%. Moreover, we demonstrate a wearable thermoelectric shoe based on antifreezing thermogalvanic hydrogels for harvesting human thermal energy in a simulated winter environment of -30 °C, and the electricity can drive a green LED. This work provides important guidance for the design and optimization of antifreezing thermogalvanic hydrogels.

9.
ACS Nano ; 17(20): 20299-20307, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37831602

RESUMEN

Thermal management textiles provide an energy-efficient strategy for personal thermal comfort by regulating heat flow between the human body and the environment. However, textiles with a single heating or cooling mode cannot realize temperature regulation under dynamic weather. Furthermore, monocolor textiles do not satisfy aesthetic requirements in a garment. Here, we develop a thermochromic (TC) conductive fiber with a coaxial structure composed of a conductive core and thermochromic shell. The TC conductive fiber-woven fabric has the ability of low-energy dynamic thermal management by combining Joule heating and modulation of solar absorption. Compared with commercial white fabrics, TC conductive fabrics exhibit a maximum temperature drop of 2.5 K, while the temperature of colored commercial fabrics is 7.5-16 K higher than that of commercial white fabrics in the hot. In the cold, the combination of Joule heating and the photothermal effect can provide desired thermal comfort for humans. Meanwhile, heat obtained from solar absorption brings the temperature of a fabric to a predetermined level, which saves energy of 625 W/m2 compared to a conductive-fiber-based textile. In addition, TC conductive fabrics with trichromatic evolution provide a sensitive and instant temperature visualization capable of identification of invisible and intense infrared radiation. These results provide another path to expand potential applications of wearable, flexible electronics.

10.
Mol Cell Endocrinol ; 578: 112076, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37769867

RESUMEN

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age and is a significant cause of female subfertility. Our previous research demonstrated that the abnormal palmitoylation of heat shock protein-90α (HSP90α) plays a role in the development of PCOS. However, the palmitoyl acyltransferases in HSP90α palmitoylation remain poorly understood. Herein, we identified ZDHHC17 as a major palmitoyl acyltransferase for HSP90α palmitoylation in granulosa cells. ZDHHC17 protein expression was diminished under excess androgen conditions in vitro and in vivo. Consistently, ovarian ZDHHC17 expression was found to be attenuated in patients with PCOS. ZDHHC17 depletion decreased HSP90α palmitoylation levels and hampered the conversion of androgen to estrogen via CYP19A1. Furthermore, ZDHHC17-mediated regulation of CYP19A1 expression was dependent on HSP90α palmitoylation. Our findings reveal that the regulatory role of HSP90α palmitoylation by ZDHHC17 is critical in PCOS pathophysiology and provide insights into the role of ZDHHC17 in reproductive endocrinology.

11.
Geroscience ; 2023 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-37532927

RESUMEN

Female infertility due to declining oocyte quality with age remains a significant challenge for patients and physicians, despite extensive research efforts. Recent studies suggest that microRNAs (miRNAs), which respond to various stressors in the aging process, may provide a promising solution. With the approval of small RNA drugs for clinical use, miRNA-based treatment of oocyte aging appears to be a viable option. Through high-throughput sequencing, miR-425-5p was identified as the only miRNA elevated under natural aging and oxidative stress. Microinjection of inhibitors to inhibit miR-425-5p effectively improved compromised phenotypes of old oocytes in vitro. Further investigation revealed that Crebzf acts as a mediator of miR-425-5p's age-related functions in old oocytes. In vivo treatment with miR-425-5p antagomirs significantly improved impaired oocyte development in reproductively old females by targeting Crebzf. Single-cell RNA sequencing revealed that Crebzf plays a vital role in regulating mRNAs targeting histone H3, trimethylated lysine 4 (H3K4me3), a crucial marker for transcriptional silencing. Overexpression of miR-425-5p could hinder oocyte maturation by downregulating Crebzf expression and disrupting transcriptional regulation. Our findings provide new insights into the potential of miR-425-5p antagomirs as a treatment for female infertility and highlight an elegant mechanism by which miR-425-5p inhibition of Crebzf inhibits a developmental switch in GV oocytes by regulating a group of histone methyltransferase mRNAs.

12.
Reprod Biomed Online ; 47(4): 103238, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37573751

RESUMEN

RESEARCH QUESTION: Is early embryo development in mice influenced by RNA binding protein with multiple splicing 2 (RBPMS2), a maternal factor that accumulates and is stored in the cytoplasm of mature oocytes? DESIGN: The expression patterns of RBPMS2 in mouse were analysed using quantitative real-time PCR (qRT PCR) and immunofluorescence staining. The effect of knockdown of RBPMS2 on embryo development was evaluated through a microinjection of specific morpholino or small interfering RNA. RNA sequencing was performed for mechanistic analysis. The interaction between RBPMS2 and the bone morphogenetic protein (BMP) pathway was studied using BMP inhibitor and activator. The effect on the localization of E-cadherin was determined by immunofluorescence staining. RESULTS: Maternal protein RBPMS2 is highly expressed in mouse oocytes, and knockdown of RBPMS2 inhibits embryo development from the morula to the blastocyst stage. Mechanistically, RNA sequencing showed that the differentially expressed genes were enriched in the transforming growth factor-ß (TGF-ß) signalling pathway. BMPs are members of the TGF-ß superfamily of growth factors. It was found that the addition of BMP inhibitor to the culture medium led to a morula-stage arrest, similar to that seen in RBPMS2 knockdown embryos. This morula-stage arrest defect caused by RBPMS2 knockdown was partially rescued by BMP activator. Furthermore, the localization of E-cadherin to the membrane was impaired in response to a knockdown of RBPMS2 or inhibition of the BMP pathway. CONCLUSION: This study suggests that RBPMS2 activates the BMP pathway and thus influences the localization of E-cadherin, which is important for early mouse embryo development during blastocyst formation.


Asunto(s)
Proteínas Morfogenéticas Óseas , Desarrollo Embrionario , Animales , Ratones , Blastocisto/metabolismo , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/metabolismo , Desarrollo Embrionario/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Factor de Crecimiento Transformador beta/metabolismo
13.
J Ovarian Res ; 16(1): 138, 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37443082

RESUMEN

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. METHODS: We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. RESULTS: We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1ß, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. CONCLUSION: These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.


Asunto(s)
Suplementos Dietéticos , Ácidos Grasos Omega-3 , Microbioma Gastrointestinal , Síndrome del Ovario Poliquístico , Animales , Femenino , Ratones , Deshidroepiandrosterona/toxicidad , Microbioma Gastrointestinal/fisiología , Resistencia a la Insulina , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/fisiopatología , Ácidos Grasos Omega-3/uso terapéutico
14.
Cell Death Discov ; 9(1): 163, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37188682

RESUMEN

In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging.

15.
Adv Mater ; 35(32): e2300696, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37222174

RESUMEN

Thermocells can continuously convert heat into electricity, and they are widely used to power wearable electronic devices. However, they have a risk of leakage and poor mechanical properties. Although quasi-solid ionic thermocells can overcome the issue of electrolyte leakage, the trade-off between their excellent mechanical properties and high thermopower remains a major challenge. In this study, stretching-induced crystallization and the thermoelectric effect are combined to propose a high-strength quasi-solid stretchable polyvinyl alcohol thermogalvanic thermocell (SPTC) with a large tensile strength of 19 MPa and high thermopower of 6.5 mV K-1 . The SPTC exhibits a high stretchability of 1300%, ultrahigh toughness of 163.4 MJ m-3 , and high specific output power density of 1969 µW m-2  K-2 . These comprehensive properties are superior to those of previously reported quasi-solid stretchable thermogalvanic thermocells. The use of SPTC-based systems in wearable devices for energy-autonomous strain sensors and health monitoring is demonstrated. This can facilitate the rapid implementation of sustainable wearable electronics in the Internet of Things era.

16.
J Ovarian Res ; 16(1): 87, 2023 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-37120599

RESUMEN

n-3 PUFAs are classic antioxidant that can be used to treat follicular dysplasia and hyperinsulinemia caused by excessive oxidative stress in PCOS women. To investigate the effect of n-3 PUFA supplementation on the oocyte quality of polycystic ovary syndrome (PCOS) mice during in vitro maturation, a PCOS mouse model was established by dehydroepiandrosterone (DHEA). The GV oocytes of the control and PCOS groups were collected and cultured in vitro with or without n-3 PUFAs. After 14 h, the oocytes were collected. Our data demonstrated that the oocyte maturation rate of PCOS mice significantly increased after the addition of 50 µM n-3 PUFAs. The results of immunofluorescence showed that the abnormal rates of spindles and chromosomes in the PCOS + n-3 PUFA group were lower than those in the PCOS group. The mRNA expression of an antioxidant-related gene (Sirt1) and DNA damage repair genes (Brca1/Msh2) was found to be significantly rescued after n-3 treatment. Additionally, the results of living cell staining showed that the addition of n-3 PUFAs could reduce the levels of reactive oxygen species and mitochondrial superoxide in PCOS oocytes. In conclusion, the addition of 50 µM n-3 PUFAs during the in vitro maturation of PCOS mouse oocytes can improve the maturation rate by reducing the level of oxidative stress and the rate of spindle/chromosome abnormalities, providing valuable support during the IVM process.


Asunto(s)
Ácidos Grasos Omega-3 , Síndrome del Ovario Poliquístico , Humanos , Femenino , Animales , Ratones , Técnicas de Maduración In Vitro de los Oocitos , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/metabolismo , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Oocitos/metabolismo , Suplementos Dietéticos
17.
iScience ; 26(3): 106131, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36879822

RESUMEN

Ovarian granulosa cells (GCs) in the follicle are the important mediator of steroidogenesis and foster oocyte maturation. Evidences suggested that the function of GCs could be regulated by S-palmitoylation. However, the role of S-palmitoylation of GCs in ovarian hyperandrogenism remains elusive. Here, we demonstrated that the protein from GCs in ovarian hyperandrogenism phenotype mouse group exhibits lower palmitoylation level compared with that in the control group. Using S-palmitoylation-enriched quantitative proteomics, we identified heat shock protein isoform α (HSP90α) with lower S-palmitoylation levels in ovarian hyperandrogenism phenotype group. Mechanistically, S-palmitoylation of HSP90α modulates the conversion of androgen to estrogens via the androgen receptor (AR) signalling pathway, and its level is regulated by PPT1. Targeting AR signaling by using dipyridamole attenuated ovarian hyperandrogenism symptoms. Our data help elucidate ovarian hyperandrogenism from perspective of protein modification and provide new evidence showing that HSP90α S-palmitoylation modification might be a potential pharmacological target for ovarian hyperandrogenism treatment.

18.
Adv Mater ; 35(15): e2209181, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36690602

RESUMEN

More than 55% of electronic failures are caused by damage from localized overheating. Up to now, there is still no efficient method for targeted temperature control against localized overheating. Although some existing thermal management devices handle this issue by full coverage cooling, it generates a lot of useless energy consumption. Here, a highly efficient pixel-matrix electrocaloric (EC) cooling device is reported, which can realize a targeted and differential thermal management. The modified poly(vinylidene fluoride-tertrifluoroethylene-chlorofluoroethylene) reaches a large adiabatic temperature change of 7.8 K and is more suitable for thermal transfer and electrostatic actuation at high frequencies. All active pixels in the EC cooling device exhibit a stable temperature span of 4.6 K and a heat flux of 62 mW cm-2 , which is more than twice that of the one-layer EC device. Each refrigeration pixel can be independently controlled and effectively cooled down the localized overheating site(s) in situ. The surface temperature of the simulated central processing unit decreases by 33.2 K at 120 s after applying this EC device. Such a compact, embeddable, low cost, and active solid-state pixel-matrix cooling device has great potential for localized overheating protection in microelectronics.

19.
Toxicol Lett ; 376: 1-12, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36642205

RESUMEN

As a widespread environmental contaminant, short chain chlorinated paraffins (SCCPs) has attracted great attention. However, the toxicity of SCCPs on male reproductive system remains ambiguous. In this study, we treated mice with SCCPs by gavage and investigated the toxic effects of SCCPs on testis. According to the results, the sperm parameters of mice were significantly reduced after exposure to 1, 10, 100 mg/kg body mass per day SCCPs for 35 days. SCCPs resulted in disorderly arranged seminiferous epithelium and increased apoptotic cells in testes. Both in vivo and in vitro experiments indicated that the oxidative stress was induced after SCCPs exposure, and dysfunction of nuclear factor erythroid-related factor (NRF2) signaling pathway played a role in this process. Moreover, resveratrol, an NRF2 activator, could alleviate the damage of SCCPs onmale reproductive system. Our study indicated that oxidative stress is the key point for explaining the testicular toxicity caused by SCCPs, and NRF2 could be used as a potential target for clinical treatment to alleviate the reproductive toxicity induced by SCCPs.


Asunto(s)
Hidrocarburos Clorados , Parafina , Animales , Masculino , Ratones , China , Monitoreo del Ambiente/métodos , Hidrocarburos Clorados/toxicidad , Factor 2 Relacionado con NF-E2/genética , Parafina/toxicidad , Parafina/análisis , Semen/química , Testículo , Estrés Oxidativo
20.
Proc Natl Acad Sci U S A ; 119(38): e2207353119, 2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-36095218

RESUMEN

Radiative thermal management provides a zero-energy strategy to reduce the demands of fossil energy for active thermal management. However, whether solar heating or radiative cooling, one-way temperature control will exacerbate all-season energy consumption during hot summers or cold winters. Inspired by the Himalayan rabbit's hair and Mimosa pudica's leaves, we proposed a dual-mode thermal-management device with two differently selective electromagnetic spectrums. The combination of visible and infrared "thermochromism" enables this device to freely switch between solar heating and radiative cooling modes by spontaneously perceiving the temperature without any external energy consumption. Numerical prediction shows that a dual-mode device exhibits an outstanding potential for all-season energy saving in terms of thermal management beyond most static or single-wavelength, range-regulable, temperature-responsive designs. Such a scalable and cost-efficient device represents a more efficient radiative thermal-management strategy toward applying in a practical scenario with dynamic daily and seasonal variations.

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