The GgcxK325Q Mutation Does Not Affect the Calcium Homeostasis of the Epididymis and Male Fertility in Mice.

A low-calcium microenvironment is imperative for spermatozoa maturation within the epididymis. Our previous work has shown that γ-glutamyl carboxylase (GGCX), the carboxylation enzyme of the matrix Gla protein (MGP), plays an essential role in epididymal calcium homeostasis and sperm maturation in rats and that the GGCX SNP mutation rs699664 was associated with asthenozoospermia (AZS) in humans. Here, we investigated the expression patterns of GGCX and MGP in the mouse epididymis and generated GgcxK325Q knock-in (KI) mice. We also tested the effects of this mutation on epididymal calcium homeostasis, sperm function, and male fertility in GgcxK325Q-/- mice. The results showed that both GGCX and MGP were enriched in all regions of the mouse epididymis, especially in the initial segment of the epididymis. Double immunofluorescence staining revealed that GGCX colocalized with MGP in the epithelial cells of the initial segment and caput regions as well as in the lumen of the corpus and cauda regions of the mouse epididymis. However, the GgcxK325Q-/- mice were fertile with normal epididymal morphology, sperm functions, and epididymal calcium concentration. Overall, our findings revealed that the GgcxK325Q mutation does not exert any discernible effect on male fertility in mice.

Novel targets and therapies of metformin in dementia: old drug, new insights.

Dementia is a devastating disorder characterized by progressive and persistent cognitive decline, imposing a heavy public health burden on the individual and society. Despite numerous efforts by researchers in the field of dementia, pharmacological treatments are limited to relieving symptoms and fail to prevent disease progression. Therefore, studies exploring novel therapeutics or repurposing classical drugs indicated for other diseases are urgently needed. Metformin, a first-line antihyperglycemic drug used to treat type 2 diabetes, has been shown to be beneficial in neurodegenerative diseases including dementia. This review discusses and evaluates the neuroprotective role of metformin in dementia, from the perspective of basic and clinical studies. Mechanistically, metformin has been shown to improve insulin resistance, reduce neuronal apoptosis, and decrease oxidative stress and neuroinflammation in the brain. Collectively, the current data presented here support the future potential of metformin as a potential therapeutic strategy for dementia. This study also inspires a new field for future translational studies and clinical research to discover novel therapeutic targets for dementia.

Metastasis-associated protein 1 participates in regulating luminal acidification of the epididymis via repressing estrogen receptor alpha transcription.

BACKGROUND: As a component of the nucleosome remodeling and deacetylating (NuRD) complex, metastasis-associated protein 1 (MTA1) has been reported to be abundant in male reproductive system and might participate in spermatogenesis and sperm maturation, whereas the precise functional role of MTA1 in these processes is still undetermined. OBJECTIVE: To investigate the effect and potential function of MTA1 in male fertility. MATERIALS AND METHODS: Mta1 knockout mice (Mta1-/- ) were employed to detect their reproductive phenotype. The pH value of Mta1-/- epididymal luminal fluid was measured, and the potential mechanism of MTA1 involved in regulating luminal acidification was detected in vivo and in vitro. A vasectomy model with abnormal pH of epididymal lumen was established to further detect the effect of MTA1 on epididymal luminal microenvironment. RESULTS: Mta1-/- mice were fertile without any detectable defects in spermatogenesis or sperm motility while the deficiency of MTA1 could acidify the initial segment of epididymis to a certain extent. MTA1 could interact with estrogen receptor alpha (ERα) and inhibit the transcription of ERα target gene, hydrogen exchanger 3 (NHE3), and ultimately affect the epididymal luminal milieu. After vasectomy, the Mta1-/- mice presented a more acidic epididymal lumen which was closer to the normal state compared to the wild-type model. DISCUSSION AND CONCLUSION: MTA1 is dispensable for male fertility in mice, but plays a potentially important function in regulating luminal acidification of the epididymis.

The design of dual-switch fluorescence intensity ratio thermometry with high sensitivity and thermochromism based on a combination strategy of intervalence charge transfer and up-conversion fluorescence thermal enhancement.

Currently, the temperature sensing performances of inorganic photoluminescence materials based on fluorescence intensity ratio technology have become a research hotspot in the optical thermometry field due to their non-contact sensing, fast response and high stability. However, several problems have obstructed the development of optical temperature sensing materials, including low sensitivity and narrow temperature measurement ranges. In view of the above dilemma, a new optical thermometer La2Mo3O12:Yb3+,Pr3+ designed based on the combination strategy of intervalence charge transfer and up-conversion fluorescence thermal enhancement was developed. Under excitation at 450 nm, the thermometer can work in a range from 298 to 648 K and the relative sensitivity reaches as high as 2.000% K-1 at 648 K. Under excitation at 980 nm, the thermometer can sense temperature with a wide range from 298 to 748 K and the relative sensitivity reaches as high as 4.325% K-1 at 598 K. A dual-switch optical temperature sensing material with high-sensitivity and a wide temperature measurement range has been successfully developed. Our research design strategies will give inspiration to the research on multi-switch temperature sensing materials with high sensitivity and a wide temperature measurement range.

Trivalent Chromium Ions Doped Fluorides with Both Broad Emission Bandwidth and Excellent Luminescence Thermal Stability.

Recently, trivalent chromium ion doped phosphors have exhibited significant application potential in broadband near-infrared (NIR) phosphor-converted light-emitting diodes (pc-LEDs). However, developing an NIR phosphor with both broad emission bandwidth and excellent luminescence thermal stability is still a great challenge. Here, we demonstrate an NIR phosphor, ScF3:Cr3+, which can fulfill both conditions simultaneously. The prepared phosphors show broadband emission in the range of 700 to 1100 nm, with a full width at half-maximum (FWHM) of 140 nm peaking at 853 nm. These phosphors also demonstrate an excellent luminescence thermal stability (the emission intensity of ScF3:Cr3+ keeps 85.5% at 150 °C compared with the value at room temperature). An NIR pc-LED based on blue LED chips was fabricated and tested. The results show that the NIR pc-LED can yield strong broadband NIR emission. This work not only provides a promising phosphor for the application of NIR pc-LEDs but also has important guiding significance for effect of synthesis conditions on the luminescence properties of Cr3+-doped fluorides.