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The main purpose of this study was to evaluate the immunity, antioxidant indices, and disease resistance of quercetin in zebrafish (Danio rerio). A total of 630 fish were assigned to 21 tanks with 30 fish/tank, and they were exposed to 0, 0.01, 0.1, 1, 10, 100, and 1000 μg/L quercetin, respectively, for 56 days. Results indicated that the immune indices including acid phosphatase (ACP), myeloperoxidase (MPO), lysozyme activities, and Complement 3 (C3), C4, IgM contents were significantly higher in 1 μg/L quercetin group than these parameters in the control group (P < 0.05). TNF-α and IL-8 mRNA expressions significantly decreased as the levels of quercetin increased up to 1 μg/L and increased thereafter (P < 0.05). 1 and 10 μg/L quercetin groups showed significantly lower TNF-α and IL-8 mRNA levels than the quercetin-free group. Transforming growth factor-β and IL-10 mRNA levels showed an obviously opposite trend with TNF-α expression. The SOD, GPX, CAT, T-AOC activities, and SOD and GPX gene expression in the liver were enhanced with increasing quercetin up to 1 μg/L, and decreased thereafter. MDA contents were affected by quercetin, in which 1 and 10 μg/L quercetin had a significantly lower level than that of the control group (P < 0.05). Defensin and Leap-II mRNA expression in the liver were the highest for fish exposed to 1 μg/L quercetin. The fish that exposed to 1 μg/L quercetin also showed a significantly higher survival rate than these of fish exposed to 0, 0.01, and 1000 μg/L quercetin (P < 0.05). In conclusion, the optimal level of quercetin promotes immunostimulant properties, antioxidant indices, and disease resistance of zebrafish.

Multi-channel information encryption technology has been implemented by optical metasurfaces owing to their superior ability to control the phase, amplitude, wavelength and polarization of incident light. However, current metasurface-based multi-channel encryption technologies suffer from information leakage in non-full channel decoding processes. To better increase the security of the encrypted information, we develop a secret shared phase encoding scheme by combining a visual secret sharing scheme with a metasurface-based phase-encoding technique. Our method achieves its high-concealment through mapping the target image into a set of unrecognizable phase-only keys that are subsequently encoded by a multi-wavelength metasurface. In the decryption process, the secret information can be reconstructed only by decoding and stacking all the wavelength channels of the metasurface. At the same time, chaotic images can be extracted from the other channels without revealing any original information. The simulated results and the theoretical analysis show the strong robustness and high security of our encryption setup, which is sure to find applications in emerging optical encryption schemes.

Steroid hormones are essential in stress response, immune system regulation, and reproduction in mammals. Steroids with 3-oxo-Δ 4 structure, such as testosterone or progesterone, are catalyzed by steroid 5α-reductases (SRD5As) to generate their corresponding 3-oxo-5α steroids, which are essential for multiple physiological and pathological processes. SRD5A2 is already a target of clinically relevant drugs. However, the detailed mechanism of SRD5A-mediated reduction remains elusive. Here we report the crystal structure of PbSRD5A from Proteobacteria bacterium , a homolog of both SRD5A1 and SRD5A2, in complex with the cofactor NADPH at 2.0 Å resolution. PbSRD5A exists as a monomer comprised of seven transmembrane segments (TMs). The TM1-4 enclose a hydrophobic substrate binding cavity, whereas TM5-7 coordinate cofactor NADPH through extensive hydrogen bonds network. Homology-based structural models of HsSRD5A1 and -2, together with biochemical characterization, define the substrate binding pocket of SRD5As, explain the properties of disease-related mutants and provide an important framework for further understanding of the mechanism of NADPH mediated steroids 3-oxo-Δ 4 reduction. Based on these analyses, the design of therapeutic molecules targeting SRD5As with improved specificity and therapeutic efficacy would be possible. Steroid 5α-reductase 2 (SRD5A2), a testosterone metabolism enzyme, is implicated in human disease. Structural and biochemical analyses of PbSRD5A, a bacterial homolog, reveal SRD5A2 substrate binding pocket and provide framework for the design of new drugs targeting this enzyme.

The modulation recognition technology for acoustic signals holds significant research importance in signal demodulation and communication signal reconnaissance, serving as a crucial component and key aspect. This paper investigates the modulation recognition technology for acoustic signals (< 20 kHz) from the perspectives of signal preprocessing and feature extraction. Firstly, it selects seven modulation signals 2ASK, 4ASK, 2FSK, 4FSK, 2PSK, 4PSK, and OFDM as recognition targets and systematically compares the effectiveness of four different endpoint detection algorithms in modulation signal recognition. To further enhance the performance of the short-time energy entropy ratio algorithm, this study introduces three different noise reduction algorithms for optimization. Finally, to accurately identify and distinguish between 2 and 4FSK signals, this study optimizes the related algorithms of the cyclic spectrum by using the kurtosis coefficient value Kur of the cyclic spectrum parameter matrix when the cyclic frequency α  =  0 to differentiate between these two signals. The results show that at SNR of 4 dB, the proposed modulation recognition algorithm can effectively distinguish between these two signals, achieving a recognition accuracy of over 99%.

The prostate cancer drug abiraterone can be metabolized into several substances with different effects, and optimization of this process could be helpful for fine-tuning the treatment of prostate cancer. Manipulating antitumour activity of abiraterone The anti-androgen prostate cancer drug abiraterone is metabolized in the body to Δ4-abiraterone (D4A), a more potent steroid than abiraterone with structural similarities to endogenous steroidal 5α-reductase substrates, such as testosterone. These authors show that D4A is converted in the body to at least six previously unrecognized metabolites with a range of different metabolic effects. In a clinical trial of abiraterone alone, followed by abiraterone plus the 5α-reductase inhibitor dutasteride, production of a downstream tumour-promoting metabolite was blocked and D4A concentrations rose. These findings suggest a previously unappreciated method of clinically fine-tuning abiraterone metabolism to optimize cancer therapy. Abiraterone blocks androgen synthesis and prolongs survival in patients with castration-resistant prostate cancer, which is otherwise driven by intratumoral androgen synthesis 1 , 2 . Abiraterone is metabolized in patients to Δ 4 -abiraterone (D4A), which has even greater anti-tumour activity and is structurally similar to endogenous steroidal 5α-reductase substrates, such as testosterone 3 . Here, we show that D4A is converted to at least three 5α-reduced and three 5β-reduced metabolites in human serum. The initial 5α-reduced metabolite, 3-keto-5α-abiraterone, is present at higher concentrations than D4A in patients with prostate cancer taking abiraterone, and is an androgen receptor agonist, which promotes prostate cancer progression. In a clinical trial of abiraterone alone, followed by abiraterone plus dutasteride (a 5α-reductase inhibitor), 3-keto-5α-abiraterone and downstream metabolites were depleted by the addition of dutasteride, while D4A concentrations rose, showing that dutasteride effectively blocks production of a tumour-promoting metabolite and permits D4A accumulation. Furthermore, dutasteride did not deplete the three 5β-reduced metabolites, which were also clinically detectable, demonstrating the specific biochemical effects of pharmacological 5α-reductase inhibition on abiraterone metabolism. Our findings suggest a previously unappreciated and biochemically specific method of clinically fine-tuning abiraterone metabolism to optimize therapy.

Histone methylation has an important role in transcriptional regulation. However, unlike H3K4 and H3K9 methylation, the role of H4K20 monomethylation (H4K20me-1) in transcriptional regulation remains unclear. Here, we show that Wnt3a specifically stimulates H4K20 monomethylation at the T cell factor (TCF)-binding element through the histone methylase SET8. Additionally, SET8 is crucial for activation of the Wnt reporter gene and target genes in both mammalian cells and zebrafish. Furthermore, SET8 interacts with lymphoid enhancing factor-1 (LEF1)/TCF4 directly, and this interaction is regulated by Wnt3a. Therefore, we conclude that SET8 is a Wnt signaling mediator and is recruited by LEF1/TCF4 to regulate the transcription of Wnt-activated genes, possibly through H4K20 monomethylation at the target gene promoters. Our findings also indicate that H4K20me-1 is a marker for gene transcription activation, at least in canonical Wnt signaling.

Prostate cancer is driven by androgen stimulation of the androgen receptor (AR). The next-generation AR antagonist, enzalutamide, prolongs survival, but resistance and lethal disease eventually prevail. Emerging data suggest that the glucocorticoid receptor (GR) is upregulated in this context, stimulating expression of AR-target genes that permit continued growth despite AR blockade. However, countering this mechanism by administration of GR antagonists is problematic because GR is essential for life. We show that enzalutamide treatment in human models of prostate cancer and patient tissues is accompanied by a ubiquitin E3-ligase, AMFR, mediating loss of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), which otherwise inactivates cortisol, sustaining tumor cortisol concentrations to stimulate GR and enzalutamide resistance. Remarkably, reinstatement of 11β-HSD2 expression, or AMFR loss, reverses enzalutamide resistance in mouse xenograft tumors. Together, these findings reveal a surprising metabolic mechanism of enzalutamide resistance that may be targeted with a strategy that circumvents a requirement for systemic GR ablation.

Background Varicella zoster virus (VZV) can remain lifelong in the latent state in ganglionic neurons and adrenal glands after the initial infection. However, it can be reactivated anytime and can trigger several severe neurological manifestations such as encephalitis, meningitis, Ramsay-Hunt syndrome, cerebellitis, myelitis, and stroke. In addition, due to the diversity of clinical manifestations, clinical diagnosis of VZV can be difficult, especially in the absence of varicella. Here, we describe the case of a 52-year-old male who presented with symptoms of acute myelitis as well as polycranial neuritis, and was finally diagnosed with VZV infection through metagenomic next-generation sequencing (mNGS). Case presentation A 52-year-old male came to our hospital with complaint of headache, fever, weakness of right lower limb, abdominal distension, and hearing loss. T2-weighted MRI revealed a hyperintense lesion in the spinal cord extending from T8 to T11. In addition, enhanced MRI showed small patches and strips hyperintensities in both the spinal cord and meninges. Plain abdominal radiographs and abdominal computed tomography (CT) scan displayed air-fluid levels and incomplete bowel obstruction. Moreover, electrophysiological evaluation of the peripheral neuropathy in the extremities was found to be normal. Finally, by using metagenomic next-generation sequencing (mNGS) we found that the copy number of VZV DNA in cerebrospinal fluid (CSF) was significantly increased and IgG antibody against VZV in CSF was also noted to be positive. Hence, VZV infection was identified in patient’s central neuron system. Finally, after a few days of low dose steroid treatment, the patient's symptoms were found to be significantly improved. Conclusions The findings indicate that we should pay proper attention to the various symptoms caused by VZV infection due to the clinical heterogeneity, especially in the absence of cutaneous lesions.

Recent achievements in amorphous/crystalline silicon heterojunction (SHJ) solar cells and perovskite/SHJ tandem solar cells place hydrogenated amorphous silicon (a-Si:H) at the forefront of photovoltaics. Due to the extremely low effective doping efficiency of trivalent boron in amorphous tetravalent silicon, light harvesting of aforementioned devices is limited by their fill factors (FFs), a direct metric of the charge carrier transport. It is challenging but crucial to develop highly conductive doped a-Si:H with minimal FF losses. Here we report that light soaking can efficiently boost the dark conductance of boron-doped a-Si:H thin films. Light induces diffusion and hopping of weakly bound hydrogen atoms, which activates boron doping. The effect is reversible and the dark conductivity decreases over time when the solar cell is no longer illuminated. By implementing this effect to SHJ solar cells, we achieved a certified total-area power conversion efficiency of 25.18% with a FF of 85.42% on a 244.63 cm 2 wafer. Low effective doping of boron limits the performance of solar cells based on hydrogenated amorphous silicon. Liu et al. show that light induces the diffusion of hydrogen atoms, which activates boron doping, enabling a power conversion efficiency of over 25%.

Strategies beyond hormone-related therapy need to be developed to improve prostate cancer mortality. Here, we show that FUBP1 and its methylation were essential for prostate cancer progression, and a competitive peptide interfering with FUBP1 methylation suppressed the development of prostate cancer. FUBP1 accelerated prostate cancer development in various preclinical models. PRMT5-mediated FUBP1 methylation, regulated by BRD4, was crucial for its oncogenic effect and correlated with earlier biochemical recurrence in our patient cohort. Suppressed prostate cancer progression was observed in various genetic mouse models expressing the FUBP1 mutant deficient in PRMT5-mediated methylation. A competitive peptide, which was delivered through nanocomplexes, disrupted the interaction of FUBP1 with PRMT5, blocked FUBP1 methylation, and inhibited prostate cancer development in various preclinical models. Overall, our findings suggest that targeting FUBP1 methylation provides a potential therapeutic strategy for prostate cancer management.