Exploring novel function of Gpx5 antioxidant activity: Assisting epididymal cells secrete functional extracellular vesicles.

Glutathione peroxisomal-5 (Gpx5) promotes the elimination of H2O2 or organic hydrogen peroxide, and plays an important role in the physiological process of resistance to oxidative stress (OS). To directly and better understand the protection of Gpx5 against OS in epididymal cells and sperm, we studied its mechanism of antioxidant protection from multiple aspects. To more directly investigate the role of Gpx5 in combating oxidative damage, we started with epididymal tissue morphology and Gpx5 expression profiles in combination with the mouse epididymal epithelial cell line PC1 (proximal caput 1) expressing recombinant Gpx5. The Gpx5 is highly expressed in adult male epididymal caput, and its protein signal can be detected in the sperm of the whole epididymis. Gpx5 has been shown to alleviate OS damage induced by 3-Nitropropionic Acid (3-NPA), including enhancing antioxidant activity, reducing mitochondrial damage, and suppressing cell apoptosis. Gpx5 reduces OS damage in PC1 and maintains the well-functioning extracellular vesicles (EVs) secreted by PC1, and the additional epididymal EVs play a role in the response of sperm to OS damage, including reducing plasma membrane oxidation and death, and increasing sperm motility and sperm-egg binding ability. Our study suggests that GPX5 plays an important role as an antioxidant in the antioxidant processes of epididymal cells and sperm, including plasma membrane oxidation, mitochondrial oxidation, apoptosis, sperm motility, and sperm-egg binding ability.

Paternal obesity induces subfertility in male offspring by modulating the oxidative stress-related transcriptional network.

BACKGROUND/OBJECTIVE: The effects of fathers' high-fat diet (HFD) on the reproductive health of their male offspring (HFD- F1) remain to be elucidated. Parental obesity is known to have a negative effect on offspring fertility, but there are few relevant studies on the effects of HFD-F1 on reproductive function. METHODS: We first succeeded in establishing the HFD model, which provides a scientific basis in the analysis of HFD-F1 reproductive health. Next, we assessed biometric indices, intratesticular cellular status, seminiferous tubules and testicular transcriptomic homeostasis in HFD-F1. Finally, we examined epididymal (sperm-containing) apoptosis, as well as antioxidant properties, motility, plasma membrane oxidation, DNA damage, and sperm-egg binding in the epididymal sperm. RESULTS: Our initial results showed that HFD-F1 mice had characteristics similar to individuals with obesity, including higher body weight and altered organ size. Despite no major changes in the types of testicular cells, we found decreased activity of important genes and noticed the presence of abnormally shaped sperm at seminiferous tubule lumen. Further analysis of HFD-F1 testes suggests that these changes might be caused by increased vulnerability to oxidative stress. Finally, we measured several sperm parameters, these results presented HFD-F1 offspring exhibited a deficiency in antioxidant properties, resulting in damaged sperm mitochondrial membrane potential, insufficient ATP content, increased DNA fragmentation, heightened plasma membrane oxidation, apoptosis-prone and decreased capacity for sperm-oocyte binding during fertilization. CONCLUSION: HFD- F1 subfertility arises from the susceptibility of the transcriptional network to oxidative stress, resulting in reduced antioxidant properties, motility, sperm-egg binding, and elevated DNA damage. Schematic representation of the HFD-F1 oxidative stress susceptibility to subfertility. Notably, excessive accumulation of ROS surpasses the physiological threshold, thereby damaging PUFAs within the sperm plasma membrane. This oxidative assault affects crucial components such as mitochondria and DNA. Consequently, the sperm's antioxidant defense mechanisms become compromised, leading to a decline in vitality, motility, and fertility.

Arginine Biosynthesis Mediates Wulingzhi Extract Resistance to Busulfan-Induced Male Reproductive Toxicity.

Busulfan, an indispensable medicine in cancer treatment, can cause serious reproductive system damage to males as a side effect of its otherwise excellent therapeutic results. Its widespread use has also caused its accumulation in the environment and subsequent ecotoxicology effects. As a Chinese medicine, Wulingzhi (WLZ) has the effects of promoting blood circulation and improving female reproductive function. However, the potential effects of WLZ in male reproduction and in counteracting busulfan-induced testis damage, as well as its probable mechanisms, are still ambiguous. In this study, busulfan was introduced in a mouse model to evaluate its production of the testicular damage. The components of different WLZ extracts were compared using an untargeted metabolome to select extracts with greater efficacy, which were further confirmed in vivo. Here, we demonstrate abnormal spermatogenesis and low sperm quality in busulfan-injured testes. The WLZ extracts showed a strong potential to rehabilitate the male reproductive system; this effect was more prominent in room-temperature extracts. Additionally, both water and ethanol WLZ extracts at room temperature alleviated various busulfan-induced adverse effects. In particular, WLZ recovered spermatogenesis, re-activated arginine biosynthesis, and alleviated the increased oxidative stress and inflammation in the testis, ultimately reversing the busulfan-induced testicular injury. Collectively, these results suggest a promising approach to protecting the male reproductive system from busulfan-induced adverse side effects, as well as those of other similar anti-cancer drugs.

Seasonal modulation of the testis transcriptome reveals insights into hibernation and reproductive adaptation in Onychostoma macrolepis.

The Onychostoma macrolepis have a unique survival strategy, overwintering in caves and returning to the river for reproduction in summer. The current knowledge on the developmental status of its testes during winter and summer is still undiscovered. We performed RNA-seq analysis on O. macrolepis testes between January and June, using the published genome (NCBI, ASM1243209v1). Through KEGG and GO enrichment analysis, we were able to identify 2111 differentially expressed genes (DEGs) and demonstrate their functions in signaling networks associated with the development of organism. At the genomic level, we found that during the overwintering phase, genes associated with cell proliferation (ccnb1, spag5, hdac7) were downregulated while genes linked to testicular fat metabolism (slc27a2, scd, pltp) were upregulated. This indicates suppression of both mitosis and meiosis, thereby inhibiting energy expenditure through genetic regulation of testicular degeneration. Furthermore, in January, we observed the regulation of autophagy and apoptosis (becn1, casp13), which may have the function of protecting reproductive organs and ensuring their maturity for the breeding season. The results provide a basis for the development of specialized feed formulations to regulate the expression of specific genes, or editing of genes during the fish egg stage, to ensure that the testes of O. macrolepis can mature more efficiently after overwintering, thereby enhancing reproductive performance.

c-Myc-Targeting PROTAC Based on a TNA-DNA Bivalent Binder for Combination Therapy of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is highly aggressive with a poor clinical prognosis and no targeted therapy. The c-Myc protein is a master transcription factor and a potential therapeutic target for TNBC. In this study, we develop a PROTAC (PROteolysis TArgeting Chimera) based on TNA (threose nucleic acid) and DNA that effectively targets and degrades c-Myc. The TNA aptamer is selected in vitro to bind the c-Myc/Max heterodimer and appended to the E-box DNA sequence to create a high-affinity, biologically stable bivalent binder. The TNA-E box-pomalidomide (TEP) conjugate specifically degrades endogenous c-Myc/Max, inhibits TNBC cell proliferation, and sensitizes TNBC cells to the cyclin-dependent kinase inhibitor palbociclib in vitro. In a mouse TNBC model, combination therapy with TEP and palbociclib potently suppresses tumor growth. This study offers a promising nucleic acid-based PROTAC modality for both chemical biology studies and therapeutic interventions of TNBC.

Photo-Activated Direct Catalytic Oxidation of Gaseous Benzene with a Cu-Connected Serial Heterojunction Array of Co3 O4 /Cux O/Foam Cu Assembled via Layer upon Layer Oxidation.

The foam copper (FCu) has been first used as a promising supporting material to prepare a photo-activated catalyst of Co3 O4 /Cux O/FCu, in which the fine Co3 O4 particles are inlayed on the Cux O nanowires to form a Z-type heterojunction array connected by substrate Cu. The prepared samples have been used as a photo-activated catalyst to directly decompose gaseous benzene and the optimized Co3 O4 /Cux O/FCu demonstrates a 99.5% removal efficiency and 100% mineralizing rate within 15 min in benzene concentration range from 350 to 4000 ppm under simulate solar light irradiation. To track the reactive mechanism, a series of MOx /Cux O/FCu (M = Mn, Fe, Co, Ni, Cu, Zn) is prepared and a novel photo-activated direct catalytic oxidation route is proposed based on the comparative investigation of material properties. Moreover, the approach grew in situ via layer upon layer oxidation on FCu dedicates to the extra lasting reusability and the easy accessibility in the diverse situations. This work provides a novel strategy for the preparation of Cu connected series multidimensional heterojunction array and a promising application for the quick abatement of the high-leveled concentration gaseous benzene and its derivatives from the industrial discharged flow or the accident scene's leakage.

Sub-Hz relative linewidths from an interferometrically stabilized mid-infrared frequency comb.

Frequency combs present a unique tool for high-precision and rapid molecular spectroscopy. Difference frequency generation (DFG) of near-infrared sources is a common approach to generate passively stabilized mid-infrared combs. However, only little attention has been paid so far to precisely measure the coherence properties of such sources. Here, we investigate these using a Raman-soliton based DFG source driven by an Yb:fiber frequency comb. A heterodyne beat between the second harmonic of the phase-locked DFG comb near 4 µm and a 2 µm Tm:fiber frequency comb locked to the same optical reference is performed. Using this method, we measure the relative phase noise power spectral density of both combs. This results in a sub-Hz relative linewidth between the DFG comb and the Tm:fiber comb. We also introduce a new pump/seed delay locking mechanism based on interferometry for long-term stable intensity noise suppression.

Green space exposure on depression and anxiety outcomes: A meta-analysis.

BACKGROUND: The development of urbanization has led to emerging mental health issues. Green space was becoming increasingly important for mental health. Previous studies have demonstrated the value of green space for a variety of outcomes connected to mental health. However, uncertainty remains regarding the association between green spaces and the risk of depression and anxiety outcomes. This study aimed to integrate present evidence from observational studies to define the association of exposure to green space with depression and anxiety. METHODS: A thorough electronic search of PubMed, Web of Science and Embase database was performed. We transformed the odds ratio (OR) of different green increments into per 0.1 unit increase in normalized difference vegetation index (NDVI) and per 10% increase in percentage of green space. Cochrane's Q and I2 statistics were used to assess study heterogeneity, and random-effects models were employed to calculate combined effect estimation OR with 95% confidence intervals (CIs). Pooled analysis was completed using Stata 15.0. RESULTS: According to this meta-analysis, a 10% increase in the proportion of green space was linked to a lower risk of depression (merged OR (95% CI) = 0.963 (0.948, 0.979)) and anxiety (merged OR (95% CI) = 0.938 (0.858, 1.025)) and a 0.1 unit increase in NDVI was linked to a lower risk of depression (merged OR (95% CI) = 0.931 (0.887, 0.977)). CONCLUSIONS: Results of this meta-analysis supported improving green space exposure in preventing depression and anxiety. Higher green space exposure might be helpful for depression and anxiety disorders. Therefore, improving or preserving green space should be regarded as a promising intervention for public health.

Fast and specific enrichment and quantification of cancer-related exosomes by DNA-nanoweight-assisted centrifugation.

Exosomes are nanoscale membrane vesicles actively released by cells and play an important role in the diagnosis of cancer-related diseases. However, it is challenging to efficiently enrich exosomes from extracellular fluids. In this work, we used DNA nanostructures as "nanoweights" during centrifugation to facilitate the enrichment of cancerous exosomes in human serum. Two different DNA tetrahedral nanostructures (DTNs), each carrying a specific aptamer for exosome biomarker recognition, were incubated with clinical samples simultaneously. One DTN triggered the cross-linking of multiple target exosomes and, therefore, enabled low-speed and fast centrifugation for enrichment. The other DTN further narrowed down the target exosome subtype and initiated a hybridization chain reaction (HCR) for sensitive signal amplification. The method enabled the detection of 1.8 × 102 MCF-7-derived exosomes per microliter and 5.6 × 102 HepG2-derived exosomes per microliter, with 1000-fold higher sensitivity than conventional ELISA and 10-fold higher sensitivity than some recently reported fluorescence assays. Besides, the dual-aptamer system simultaneously recognized multiple surface proteins, eliminating the interference risk from free proteins. Thus, this easy-to-operate method can enrich exosomes with excellent specificity and sensitivity and therefore will be appealing in biomedical research and clinical diagnosis.

Long-term stable, synchronizable, low-noise picosecond Ho:fiber NALM oscillator for Ho:YLF amplifier seeding.

We demonstrate a 41.6 MHz, 1.3 ps, 140 pJ Ho:fiber oscillator using a nonlinear amplifying loop mirror (NALM) as saturable absorber. The oscillator is constructed entirely with polarization-maintaining (PM) fibers, is tunable with a center wavelength between 2035 nm and 2075 nm, and can be synchronized to an external RF reference. For our application of Ho:YLF amplifier seeding for dielectric electron acceleration, the laser is tuned to 2050 nm and synchronized to a stable RF reference with 45 fs rms timing jitter in the integration interval [10 Hz, 1 MHz]. We show long term synchronized operation and characterize the relative intensity noise (RIN) and timing jitter of the oscillator for two different Tm-fiber pump lasers.

Timing jitter reduction through relative intensity noise suppression in high-repetition-rate mode-locked fiber lasers.

We reported the timing jitter reduction of an 882 MHz mode-locked NPE Yb:fiber lasers through active relative intensity noise suppression. The timing jitter spectra measurements based on balanced optical cross-correlation (BOC) technique show a reduction of ~10 dB in the Fourier frequency range from ~3 kHz to ~30 kHz with a unity-gain crossing point of 80 kHz. The results verify the theoretical prediction that the relative intensity noise (RIN) induced timing jitter by self-steepening effect dominates the jitter performance below ~100 kHz. Further comparison with the analytic model shows that the effect of RIN decays below ~3 kHz. Thus, the timing jitter reduction is not obvious at low frequency. To the best of our knowledge, this is the first experimental report on the timing jitter reduction through active RIN suppression in high-repetition-rate mode-locked fiber lasers.

Timing jitter of high-repetition-rate mode-locked fiber lasers.

We characterize the timing jitter of the pulse trains from 880 MHz Yb-doped nonlinear polarization rotation mode-locked fiber lasers based on a balanced optical cross-correlation method. Jitter spectral density at different net-cavity dispersions has been characterized, and the near-zero dispersion shows the lowest rms timing jitter (10 fs rms, integrated from 30 kHz to 5 MHz). The measurements have been compared with analytical models. The comparison shows that the RIN-coupled timing jitter by nonlinearity is the dominated origin of the measured timing jitter below ∼100 kHz, while amplified spontaneous emission noise makes a major contribution in the high frequency range above hundreds of kilohertz. To the best of our knowledge, this is the first high-precision timing jitter characterization for the ∼gigahertz level repetition rate mode-locked fiber lasers. The results will be of great importance for further improving the laser performance for many applications.

Low-noise 750 MHz spaced ytterbium fiber frequency combs.

We demonstrate two low-noise 750 MHz ytterbium fiber frequency combs that are independently stabilized to a continuous-wave laser. A bulk electro-optic modulator and a single-stack piezo-electric transducer are employed as fast actuators for stabilizing the respective cavity length to heterodyne beat notes. Both combs exhibit in-loop fractional frequency instabilities of ∼10-18 at 1 s. To the best of our knowledge, this is the first demonstration of tightly phase-locked (<1 rad root mean square phase noise integrated from 0.1 Hz to 10 MHz) fiber frequency combs with 750 MHz fundamental repetition rate.

A Telomerase-Responsive DNA Icosahedron for Precise Delivery of Platinum Nanodrugs to Cisplatin-Resistant Cancer.

A telomerase-responsive DNA icosahedron was designed to precisely release caged platinum nanodrugs into cisplatin-resistance tumor cells for effective therapy. This DNA icosahedron was constructed from two pyramidal DNA cages connected with telomerase primers and telomeric repeats, and platinum nanodrugs were then encapsulated into the DNA structure. In the presence of telomerase, the primers are extended, leading to inner-chain substitution of the DNA icosahedron and subsequent release of the caged nanodrugs. This DNA icosahedron can precisely release caged nanodrugs in response to telomerase in tumor cells, giving enhanced anticancer efficacy in drug-resistant carcinoma and with reduced toxicity to normal tissues. We speculate that this precisely designed, well controlled DNA cage could be generalized to diverse anticancer drugs.

Fully stabilized 750-MHz Yb: fiber frequency comb.

This study focuses on presenting a fully stabilized, self-referenced Yb:fiber frequency comb respectively phase locked to a microwave standard and an optical reference employing the highest, fundamental repetition rate of 750-MHz without additional external amplifiers and compressors. In addition, the challenge of phase locking the carrier envelop offset frequency for this high-repetition-rate fiber frequency comb is separately investigated in two schemes, namely, f-2f self-referencing and an approach of phase locking a beat note between the Yb: fiber frequency comb and a continuous wave laser.

Fully stabilized 750-MHz Yb: fiber frequency comb: erratum.

A statement error was produced in the text introducing the previous literatures in [Opt. Express25, 11910 (2017)10.1364/OE.25.011910]. Here, we correct this error and clarify that this is only due to the simple editing mistake, not related to the scientific misunderstanding about the referenced literatures. Thus, all the conclusions written in [Opt. Express25, 11910 (2017)10.1364/OE.25.011910] remain unchanged by this correction.

Smart worm-like micelles responsive to CO2/N2 and light dual stimuli.

CO2/N2 and light dual stimuli-responsive worm-like micelles (WLMs) were obtained by addition of a relatively small amount of a switchable surfactant, 4-butyl-4'-(4-N,N-dimethylhexyloxy-amine) azobenzene bicarbonate (AZO-B6-CO2), sensitive to the same triggers to a binary aqueous solution of cetyltrimethylammonium bromide (CTAB) and sodium salicylate (NaSal).

Pickering Emulsions Responsive to CO2/N2 and Light Dual Stimuli at Ambient Temperature.

A dual stimuli-responsive n-octane-in-water Pickering emulsion with CO2/N2 and light triggers is prepared using negatively charged silica nanoparticles in combination with a trace amount of dual switchable surfactant, 4-butyl-4-(4-N,N-dimethylbutoxyamine) azobenzene bicarbonate (AZO-B4), as stabilizers. On one hand, the emulsion can be transformed between stable and unstable at ambient temperature rapidly via the N2/CO2 trigger, and on the other hand, a change in droplet size of the emulsion can occur upon light irradiation/rehomogenization cycles without changing the particle/surfactant concentration. The dual responsiveness thus allows for a precise control of emulsion properties. Compared with emulsions stabilized by specially synthesized stimuli-responsive particles or by stimuli-responsive surfactants, the method reported here is much easier and requires a relatively low concentration of surfactant (≈1/10 cmc), which is important for potential applications.

1 GHz repetition rate femtosecond Yb:fiber laser for direct generation of carrier-envelope offset frequency.

We report a mode-locked fiber laser working at a 1 GHz fundamental repetition rate. The laser delivers a 600 mW average power at a pump power of 1800 mW. The pulse spectrum bandwidth was 23 nm to support 64 fs near-transform-limited pulses. An octave-spanning supercontinuum from 590 to 1350 nm was generated in a tapered photonic crystal fiber solely with the mode-locked fiber-laser output, without amplifiers. A 30 dB f(ceo) beat signal was detected via f-to-2f interferometer.

Total flavonoids from Ganshanbian (Herba Hyperici Attenuati) effect the expression of CaL-alpha1C and K(ATP)-Kir6.1 mRNA of the myocardial cell membrane in myocardial ischemia-reperfusion arrhythmia rats.

OBJECTIVE: To observe the impact of total flavonoids from Ganshanbian (Herba Hyperici Attenuati) on the expression of vascular smooth muscle membrane L-type calcium channel alpha1 C subunit (CaL-alpha1C) and ATP-sensitive K+ channel (K(ATP))-Kir6.1 mRNA, and explore the mechanisms of the antiarrhythmic effect of Ganshanbian (Herba Hyperici Attenuati) total flavonoids. METHODS: The treatment group was fed total flavonoids from Ganshanbian (Herba Hyperici Attenuati) for 7 days by gavage with 100 mg x kg(-1) x d(-1). The blank control group and model control group were given the same amount of normal saline for 7 d. Arrhythmias were induced by performing a myocardial ischemia-reperfusion and electrocardiogram was observed. Reverse transcription-polymerase chain reaction was used to detect the expression of CaL-alpha 1C and K(ATP)-Kir6.1 mRNA in the myocardial cell membrane of all groups of rats. RESULTS: Total flavonoids from Ganshanbian (Herba Hyperici Attenuati) can delay the appearance of myocardial ischemia reperfusion arrhythmias, shorten the duration of myocardial ischemia reperfusion arrhythmias, reduce heart rate, reduce cell membrane expression of CaL-a1C mRNA and enhance the expression of K(ATP)-Kir6.1 mRNA in myocardial ischemia-reperfusion arrhythmic rats. CONCLUSION: Total flavonoids from Ganshanbian (Herba Hyperici Attenuati) can alleviate arrhythmias by affecting the expression of L-type calcium channels and ATP-sensitive K+ channels.