Deciphering dynamic interactions between spermatozoa and the ovarian microenvironment through integrated multi-omics approaches in viviparous black rockfish (Sebastes schlegelii).

The ovarian microenvironment plays a critical role in ensuring the reproductive success of viviparous teleosts. However, the molecular mechanism underlying the interaction between spermatozoa and the ovarian microenvironment has remained elusive. This study aimed to contribute to a better understanding to this process in black rockfish (Sebastes schlegelii) utilizing integrated multi-omics approaches. The results demonstrated significant upregulation of ovarian complement-related proteins and pattern recognition receptors, along with remodeling of glycans on the surface of spermatozoa at early spermatozoa-storage stage (one month after mating). As spermatozoa were stored over time, ovarian complement proteins were progressively repressed by tryptophan and hippurate, indicating a remarkable adaptation of spermatozoa to the ovarian microenvironment. Near fertilization, a notable upregulation of cellular junction proteins was observed. The study revealed that spermatozoa bind to ZPB2a protein through GSTM3 and that ZPB2a promoted spermatozoa survival and movement in a GSTM3-dependent manner. These findings shed light on a key mechanism influencing the dynamics of spermatozoa in the female reproductive tract, providing valuable insights into the molecular networks regulating spermatozoa adaptation and survival in species with internal fertilization.

Ultrastrong exciton-plasmon couplings in WS2 multilayers synthesized with a random multi-singular metasurface at room temperature.

Van der Waals semiconductors exemplified by two-dimensional transition-metal dichalcogenides have promised next-generation atomically thin optoelectronics. Boosting their interaction with light is vital for practical applications, especially in the quantum regime where ultrastrong coupling is highly demanded but not yet realized. Here we report ultrastrong exciton-plasmon coupling at room temperature in tungsten disulfide (WS2) layers loaded with a random multi-singular plasmonic metasurface deposited on a flexible polymer substrate. Different from seeking perfect metals or high-quality resonators, we create a unique type of metasurface with a dense array of singularities that can support nanometre-sized plasmonic hotspots to which several WS2 excitons coherently interact. The associated normalized coupling strength is 0.12 for monolayer WS2 and can be up to 0.164 for quadrilayers, showcasing the ultrastrong exciton-plasmon coupling that is important for practical optoelectronic devices based on low-dimensional semiconductors.

Extraordinary Enhancement of Nonlinear Optical Interaction in NbOBr2 Microcavities.

2D materials are burgeoning as promising candidates for investigating nonlinear optical effects due to high nonlinear susceptibilities, broadband optical response, and tunable nonlinearity. However, most 2D materials suffer from poor nonlinear conversion efficiencies, resulting from reduced light-matter interactions and lack of phase matching at atomic thicknesses. Herein, a new 2D nonlinear material, niobium oxide dibromide (NbOBr2) is reported, featuring strong and anisotropic optical nonlinearities with scalable nonlinear intensity. Furthermore, Fabry-Pérot (F-P) microcavities are constructed by coupling NbOBr2 with air holes in silicon. Remarkable enhancement factors of ≈630 times in second harmonic generation (SHG) and 210 times in third harmonic generation (THG) are achieved on cavity at the resonance wavelength of 1500 nm. Notably, the cavity enhancement effect exhibits strong anisotropic feature tunable with pump wavelength, owing to the robust optical birefringence of NbOBr2. The ratio of the enhancement factor along the b- and c-axis of NbOBr2 reaches 2.43 and 5.27 for SHG and THG at 1500 nm pump, respectively, which leads to an extraordinarily high SHG anisotropic ratio of 17.82 and a 10° rotation of THG polarization. The research presents a feasible and practical strategy for developing high-efficiency and low-power-pumped on-chip nonlinear optical devices with tunable anisotropy.

Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases.

Bovine respiratory disease (BRD) is a significant veterinary challenge, often exacerbated by pathogen resistance, hindering effective treatment. Traditional testing methods for primary pathogens - Mycoplasma bovis, Pasteurella multocida, and Mannheimia haemolytica - are notably time-consuming and lack the rapidity required for effective clinical decision-making. This study introduces a TaqMan MGB probe detection chip, utilizing fluorescent quantitative PCR, targeting key BRD pathogens and associated drug-resistant genes and sites. We developed 94 specific probes and primers, embedded into a detection chip, demonstrating notable specificity, repeatability, and sensitivity, reducing testing time to under 1 h. Additionally, we formulated probes to detect mutations in the quinolone resistance-determining region, associated with fluoroquinolone resistance in BRD pathogens. The chip exhibited robust sensitivity and specificity, enabling rapid detection of drug-resistant mutations in clinical samples. This methodology significantly expedites the diagnostic process for BRD and sensitive drug screening, presenting a practical advancement in the field.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

Semen promotes oocyte development in Sebastesschlegelii elucidating ovarian development dynamics in live-bearing fish.

In some vertebrates and invertebrates, semen release factors affecting female physiology and behavior. Here, we report that semen delivered to females is potentially beneficial for promoting oocyte development in a viviparous teleost, Sebastes schlegelii. 88% of mated ovaries develop normally and give birth to larval fish, whereas 61% of non-mated ovaries are arrested in the previtellogenic stage. Semen's significant role (p < 0.0001) in promoting oocyte development may involve remodeling follicular cells and regulating the expression of the extracellular matrix, which facilitates cell communication. Furthermore, the ovarian response to semen may influence the brain, affecting hormone release, follicular cell development and steroid production, and crucial for oocyte growth. This mechanism, which could potentially delay maternal investment in offspring until male genetic input occurs to avoid energy wastage, has not been previously described in teleosts. These findings enhance our understanding of ovarian development in viviparous fish, with broader implications for reproductive biology.

Dissecting the dynamic cellular transcriptional atlas of adult teleost testis development throughout the annual reproductive cycle.

Teleost testis development during the annual cycle involves dramatic changes in cellular compositions and molecular events. In this study, the testicular cells derived from adult black rockfish at distinct stages - regressed, regenerating and differentiating - were meticulously dissected via single-cell transcriptome sequencing. A continuous developmental trajectory of spermatogenic cells, from spermatogonia to spermatids, was delineated, elucidating the molecular events involved in spermatogenesis. Subsequently, the dynamic regulation of gene expression associated with spermatogonia proliferation and differentiation was observed across spermatogonia subgroups and developmental stages. A bioenergetic transition from glycolysis to mitochondrial respiration of spermatogonia during the annual developmental cycle was demonstrated, and a deeper level of heterogeneity and molecular characteristics was revealed by re-clustering analysis. Additionally, the developmental trajectory of Sertoli cells was delineated, alongside the divergence of Leydig cells and macrophages. Moreover, the interaction network between testicular micro-environment somatic cells and spermatogenic cells was established. Overall, our study provides detailed information on both germ and somatic cells within teleost testes during the annual reproductive cycle, which lays the foundation for spermatogenesis regulation and germplasm preservation of endangered species.

SirT7-mediated transcription of fascin in hyperglycemic glomerular endothelial cells contributes to EndMT in diabetic nephropathy.

Diabetic nephropathy (DN) is the main cause of end-stage renal disease worldwide. It is reported that the endothelial-to-mesenchymal transition (EndMT) in glomerular endothelial cells plays an important role in DN. As a specific form of epithelial-to-mesenchymal transition, EndMT may involve common regulators of epithelial-to-mesenchymal transition. Fascin has been shown to mediate epithelial-to-mesenchymal transition. In addition, SirT7 has been confir med to contribute to inflammation in hyperglycemic endothelial cells via the modulation of gene transcription. In this study, we speculate that SirT7 modulates fascin transcription and is thus involved in EndMT in hyperglycemic glomerular endothelial cells. Our data indicate that α-smooth muscle actin (α-SMA) and fascin levels are increased, while CD31 levels are decreased in the kidneys of DN rats. Consistently, our cellular experiments reveal that high glucose treatment elevates fascin levels and induces EndMT in human glomerular endothelial cells (HGECs). Moreover, silencing of fascin inhibits EndMT in hyperglycaemic HGECs. In addition, SirT7 is found to be decreased in hyperglycemic cells and in the kidneys of DN mice. Moreover, the inhibition of SirT7 increases fascin level and mediates EndMT. An increase in SirtT7 expression decreases fascin expression, inhibits EndMT, and improves renal function in hyperglycemic cells and DN mice. SirT7 is found to bind to the promoter region of fascin. In summary, the present study indicates that SirT7 transcribes fascin to contribute to hyperglycemia-induced EndMT in DN patients.

Insights into the Efficient Release of the Polyacrylamide Drag Reducer via a pH-Responsive Inverse Polymer Emulsion.

The enormous demand for petroleum consumption has resulted in the shortage of fossil resources, prompting the need to explore unconventional reservoirs. Polyacrylamide emulsion drag reducers are capable of inhibiting the turbulence of fracturing fluids for enhancing the reservoir stimulation results, but the poor dissolution efficiency of polyacrylamide emulsion drag reducers is the primary limitation to their large-scale application. Here, a pH-responsive ionic liquid surfactant, oleic acid/cyclohexanediamine (HOA/HMDA), is synthesized by using oleic acid (HOA) and cyclohexanediamine (HMDA). HOA/HMDA shows a remarkable pH-responsive behavior due to the pH-induced deconstruction of the HOA/HMDA structure. Interestingly, the HOA/HMDA-stabilized monomer emulsion exhibits an obvious pH-induced emulsion structure transformation behavior. In addition, the HOA/HMDA-stabilized monomer emulsion possesses excellent dynamic and storage stability, supporting the inverse emulsion polymerization of the polymer P(AM/AMPS/AA). The obtained P(AM/AMPS/AA) polymer inverse emulsions maintained stability for 30 days. Our finding proposes that the structure of the P(AM/AMPS/AA) polymer inverse emulsions changes with pH stimulation, which is capable of facilitating the release of polymers. P(AM/AMPS/AA) is released from the P(AM/AMPS/AA) polymer inverse emulsions within 30 s at a pH value of 12.06, along with a drag reduction rate of 62.54%. Obviously, the HOA/HMDA-stabilized P(AM/AMPS/AA) polymer inverse emulsions eliminate the contradiction between the stability and release of polyacrylamide emulsion drag reducers, which is promising for meeting the demands of reservoir stimulation.

Rerouting phytosterol degradation pathway for directed androst-1,4-diene-3,17-dione microbial bioconversion.

Steroid-based drugs are now mainly produced by the microbial transformation of phytosterol, and a two-step bioprocess is adopted to reach high space-time yields, but byproducts are frequently observed during the bioprocessing. In this study, the catabolic switch between the C19- and C22-steroidal subpathways was investigated in resting cells of Mycobacterium neoaurum NRRL B-3805, and a dose-dependent transcriptional response toward the induction of phytosterol with increased concentrations was found in the putative node enzymes including ChoM2, KstD1, OpccR, Sal, and Hsd4A. Aldolase Sal presented a dominant role in the C22 steroidal side-chain cleavage, and the byproduct was eliminated after sequential deletion of opccR and sal. Meanwhile, the molar yield of androst-1,4-diene-3,17-dione (ADD) was increased from 59.4 to 71.3%. With the regard of insufficient activity of rate-limiting enzymes may also cause byproduct accumulation, a chromosomal integration platform for target gene overexpression was established supported by a strong promoter L2 combined with site-specific recombination in the engineered cell. Rate-limiting steps of ADD bioconversion were further characterized and overcome. Overexpression of the kstD1 gene further strengthened the bioconversion from AD to ADD. After subsequential optimization of the bioconversion system, the directed biotransformation route was developed and allowed up to 82.0% molar yield with a space-time yield of 4.22 g·L-1·day-1. The catabolic diversion elements and the genetic overexpression tools as confirmed and developed in present study offer new ideas of M. neoaurum cell factory development for directed biotransformation for C19- and C22-steroidal drug intermediates from phytosterol. KEY POINTS: • Resting cells exhibited a catabolic switch between the C19- and C22-steroidal subpathways. • The C22-steroidal byproduct was eliminated after sequential deletion of opccR and sal. • Rate-limiting steps were overcome by promoter engineering and chromosomal integration.

Fast and Stable Antibacterial Coating of Photosensitive Aggregation-Induced Emission Luminogens for Disinfection on Medical Devices.

Aggregation-induced emission luminogens (AIEgens) are promising photosensitizers that have exhibited excellent antibacterial ability with abundant reactive oxygen species (ROS) generation. TTCPy-PF6 and TTCPy-Br are deposited on the surface of diverse solid substrates through plasma-assistant electrostatic self-assembly. The AIEgens-covered coating can effectively eliminate different pathogenic Gram-positive (G+) bacteria and even their multidrug-resistant (MDR) mutants with negligible side effects such as cytotoxicity, hemolysis, and inflammation. Moreover, the AIEgen-coated surface can maintain high stability for long-time antibacterial usage, which is dependent on the ROS-mediated disruption of the attached bacteria. The AIEgen-based coatings with broad surface applicability have many advantages in high antibacterial ability, great biocompatibility, and low possibility of antibiotic pollution. The robust antibacterial ability and excellent biological safety of the AIEgen-based coatings would be helpful for the disinfection of medical devices.

Liquid Metal-Polymer Conductor-Based Conformal Cyborg Devices.

Gallium-based liquid metal (LM) exhibits exceptional properties such as high conductivity and biocompatibility, rendering it highly valuable for the development of conformal bioelectronics. When combined with polymers, liquid metal-polymer conductors (MPC) offer a versatile platform for fabricating conformal cyborg devices, enabling functions such as sensing, restoration, and augmentation within the human body. This review focuses on the synthesis, fabrication, and application of MPC-based cyborg devices. The synthesis of functional materials based on LM and the fabrication techniques for MPC-based devices are elucidated. The review provides a comprehensive overview of MPC-based cyborg devices, encompassing their applications in sensing diverse signals, therapeutic interventions, and augmentation. The objective of this review is to serve as a valuable resource that bridges the gap between the fabrication of MPC-based conformal devices and their potential biomedical applications.

Central administration of AICAR attenuates hypertension via AMPK/Nrf2 pathway in the hypothalamic paraventricular nucleus of hypertensive rats.

BACKGROUND: Oxidative stress and inflammatory cytokines in the hypothalamus paraventricular nucleus (PVN) have been implicated in sympathetic nerve activity and the development of hypertension, but the specific mechanisms underlying their production in the PVN remains to be elucidated. Previous studies have demonstrated that activation of nuclear transcription related factor-2 (Nrf2) in the PVN reduced the production of reactive oxygen species (ROS) and inflammatory mediators. Moreover, AMP-activated protein kinase (AMPK), has been observed to decrease ROS and inflammatory cytokine production when activated in the periphery. 5-amino-1-ß-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) is an AMPK agonist. However, little research has been conducted on the role of AMPK in the PVN during hypertension. Therefore, we hypothesized that AICAR in the PVN is involved in regulating AMPK/Nrf2 pathway, affecting ROS and inflammatory cytokine expression, influencing sympathetic nerve activity. METHODS: Adult male Sprague-Dawley rats were utilized to induce two-kidney, one-clip (2K1C) hypertension via constriction of the right renal artery. Bilateral PVN was microinjected with either artificial cerebrospinal fluid or AICAR once a day for 4 weeks. RESULTS: Compared to the SHAM group, the PVN of 2K1C hypertensive rats decreased p-AMPK and p-Nrf2 expression, increased Fra-Like, NAD(P)H oxidase (NOX)2, NOX4, tumor necrosis factor-α and interleukin (IL)-1ß expression, elevated ROS levels, decreased superoxide dismutase 1 and IL-10 expression, and elevated plasma norepinephrine levels. Bilateral PVN microinjection of AICAR significantly ameliorated these changes. CONCLUSION: These findings suggest that repeated injection of AICAR in the PVN suppresses ROS and inflammatory cytokine production through the AMPK/Nrf2 pathway, reducing sympathetic nerve activity and improving hypertension.

Association between bacterial vaginosis with human papillomavirus in the United States (NHANES 2003-2004).

BACKGROUND: The balance of vaginal microecology is closely related to human papillomavirus (HPV) infection and cervical lesions. This study aims to investigate the relationship between bacterial vaginosis (BV) and HPV infection. METHODS: In total, 1,310 individuals from the National Health and Nutrition Examination Survey (NHANES, 2003-2004) were included in this study. Logistic regression and subgroup analyses were used to examine the association between BV and HPV infection. RESULTS: A significant positive association was observed between BV and HPV infection in women after adjustment for other confounders (OR = 1.47, 95% confidence interval [CI]: 1.15-1.88). In subgroup analyses, we have found this positive correlation was most prominent among Mexican Americans (OR = 1.83, 95% CI: 1.08-3.08) and non-Hispanic blacks (OR = 1.81, 95% CI: 1.08-3.04). CONCLUSIONS: This cross-sectional study demonstrated a positive association between BV and HPV infection in women.

Modal Phase-Matched Bound States in the Continuum for Enhancing Third Harmonic Generation of Deep Ultraviolet Emission.

Coherent deep ultraviolet (DUV) light sources are crucial for various applications such as nanolithography, biomedical imaging, and spectroscopy. DUV light sources can be generated by using conventional nonlinear optical crystals (NLOs). However, NLOs are limited by their bulky size, inadequate transparency at the DUV regime, and stringent phase-matching requirements for harmonic generation. Recently, dielectric metasurfaces support high Q-factor resonances and offer a promising approach for efficient harmonic generation at short wavelengths. In this study, we demonstrated a crystalline silicon (c-Si) metasurface simultaneously exciting modal phase-matched bound states in the continuum (BIC) resonance at the fundamental wavelength of 840 nm with a higher degree of freedom for precise control of the BIC resonance and a plasmonic resonance at the wavelength of 280 nm in the DUV to enhance third harmonic generation (THG). We experimentally achieved a Q-factor of ∼180 owing to the relatively large refractive index of the c-Si and the geometric symmetry breaking of the structure. We realized THG at a wavelength of 280 nm with a power of 14.5 nW by using a peak power density of 15 GW/cm2 excitation. The measured THG power is 14 times higher than the state-of-the-art THG dielectric metasurfaces using the same peak power density in the DUV regime, and the maximum obtained THG power enhancement factor is up to 48. This approach relies on the significant third-order nonlinear susceptibility of c-Si, the interband plasmonic nature of the c-Si in the DUV, and the strong field confinement of BIC resonance to boost overall nonlinear conversion efficiency to 5.2 × 10-6% in the DUV regime. Our work shows the potential of c-Si BIC metasurfaces for developing efficient and ultracompact DUV light sources using high-efficacy nonlinear optical devices.

Multidimensional detection enabled by twisted black arsenic-phosphorus homojunctions.

A light field carrying multidimensional optical information, including but not limited to polarization, intensity and wavelength, is essential for numerous applications such as environmental monitoring, thermal imaging, medical diagnosis and free-space communications. Simultaneous acquisition of this multidimensional information could provide comprehensive insights for understanding complex environments but remains a challenge. Here we demonstrate a multidimensional optical information detection device based on zero-bias double twisted black arsenic-phosphorus homojunctions, where the photoresponse is dominated by the photothermoelectric effect. By using a bipolar and phase-offset polarization photoresponse, the device operated in the mid-infrared range can simultaneously detect both the polarization angle and incident intensity information through direct measurement of the photocurrents in the double twisted black arsenic-phosphorus homojunctions. The device's responsivity makes it possible to retrieve wavelength information, typically perceived as difficult to obtain. Moreover, the device exhibits an electrically tunable polarization photoresponse, enabling precise distinction of polarization angles under low-intensity light exposure. These demonstrations offer a promising approach for simultaneous detection of multidimensional optical information, indicating potential for diverse photonic applications.

Alkane-Strengthened Viscoelasticity in Micellar Solutions of Surface-Active Ionic Liquids and Their Potential Application in Enhanced Oil Recovery.

Wormlike micelles (WLMs) are highly sensitive to alkanes, resulting in structural destruction and loss of viscosity. Therefore, the study of WLMs against alkanes holds great significant importance. Surface-active ionic liquids have shown increasing promise for different situations for customizing molecular structures with the specialty of flexible functional assembly. In this paper, we found that WLMs constructed from the long-chain fatty acid surface-active ionic liquid (N,N-dimethylbenzylamine-oleic acid, abbreviated as BD-OA) exhibit strengthened viscoelasticity with the introduction of alkanes, expanding the resistance range to alkane damage. Here, the rheological behavior, microstructure, and dissipative particle dynamics (DPD) simulations of BD-OA WLMs were investigated at macro-, micro-, and mesoscopic scales, before (and after) the introduction of alkane. Our findings confirm the structural transformation of the micellar system from WLMs to lamellar micelles with higher viscoelasticity after alkane induction. The rearrangement of the micelle configuration may be attributed to the infiltration of alkane molecules into the fence layer formed by the BD-OA WLMs, leading to an increase in the boundary accumulation parameter and ultimately resulting in the formation of lower curvature lamellar micelles. More importantly, the against alkanes BD-OA WLMs have exhibited excellent in enhanced oil recovery, which has a promise for substituting common oil-displacing agents in tertiary oil recovery processes.

Orexin receptors in paraventricular nucleus influence sexual behavior via regulating the sympathetic outflow in males.

BACKGROUND: Orexins are hypothalamic neuropeptides associated with various neurophysiological activities such as sleep, arousal, and reward. However, there are few studies investigating the relationships between orexin receptors in the paraventricular nucleus and sexual behaviors. OBJECTIVES: To explore the roles of orexin receptors in the paraventricular nucleus on sexual behaviors and uncover its potential mechanisms in males. MATERIALS AND METHODS: Orexin A, orexin 1 receptor antagonist SB334867, and orexin 2 receptor antagonist TCS-OX2-29 were microinjected into the paraventricular nucleus to investigate the effects of orexin receptors on copulatory behavior testing of C57BL/6 mice. To explore if ejaculation could activate orexin 1 receptor-expressing neurons in the paraventricular nucleus, fluorescence immunohistochemical double staining was utilized. The levels of serum norepinephrine were measured and the lumbar sympathetic nerve activity was recorded to reflect the sympathetic nervous system activity. Moreover, the bulbospongiosus muscle-electromyogram was recorded and analyzed. To test whether perifornical/lateral hypothalamic area orexinergic neurons directly projected to the paraventricular nucleus, virus retrograde tracing technology was utilized. RESULTS: Orexin A significantly enhanced sexual performance by shortening the intromission and ejaculation latencies, and increasing the mount and intromission frequencies, while the opposite outcomes appeared with SB334867. However, TCS-OX2-29 had no significant effects on sexual behaviors. Moreover, orexin A increased lumbar sympathetic nerve activity and the levels of serum norepinephrine, while SB334867 decreased lumbar sympathetic nerve activity and norepinephrine, which caused a significant decrease in sympathetic nervous system outflow. Meanwhile, a robust increase in the bulbospongiosus muscle-electromyogram activity was identified after microinjecting orexin A. Furthermore, cFos immunopositive cells were increased and double stained with orexin 1 receptor-expressing neurons in the mating group. Additionally, the retrograde tracing results demonstrated that orexinergic neurons in the perifornical/lateral hypothalamic area directly projected to the paraventricular nucleus. CONCLUSIONS: Orexin 1 receptor in the paraventricular nucleus could influence the ejaculatory reflex via mediating the sympathetic nervous system activity, which might be of great importance in the treatment of premature ejaculation in the future.

Resveratrol-derived inhibitors of the E3 ubiquitin ligase PELI1 inhibit the metastasis of triple-negative breast cancer.

Triple-negative breast cancer (TNBC), as the most challenging subtype of breast cancer, exerts highly invasive ability and metastatic nature to the lymph nodes, which is correlated with poor survival rates among patients. Pellino-1 (PELI1) is an E3 ubiquitin ligase involved in tumor invasion and metastasis, and has the potential to be developed as a novel therapeutic target for TNBC. In this study, we identified a potent inhibitor of PELI1, namely compound 3d, on the basis of natural stilbene framework through medicinal chemistry approaches. This novel PELI1 inhibitor 3d showed potent binding affinity to PELI1 (Kd 8.2 µM) in fluorescence quenching assay, and markedly interrupted the interaction of PELI1 and SNAIL/SLUG confirmed by co-immunoprecipitation. Moreover, 3d exhibited potent antitumor activity in inhibiting tumor cell migration in scratch wound healing assay without affecting cell proliferation in vitro, and down-regulated the downstream EMT-effectors of PELI1 as assessed by western blotting. In the experimental lung metastasis model, 3d showed anti-TNBC metastasis efficacy without observable toxicity in vivo.

Polyethyleneimine-coated MXene quantum dots improve cotton tolerance to Verticillium dahliae by maintaining ROS homeostasis.

Verticillium dahliae is a soil-borne hemibiotrophic fungal pathogen that threatens cotton production worldwide. In this study, we assemble the genomes of two V. dahliae isolates: the more virulence and defoliating isolate V991 and nondefoliating isolate 1cd3-2. Transcriptome and comparative genomics analyses show that genes associated with pathogen virulence are mostly induced at the late stage of infection (Stage II), accompanied by a burst of reactive oxygen species (ROS), with upregulation of more genes involved in defense response in cotton. We identify the V991-specific virulence gene SP3 that is highly expressed during the infection Stage II. V. dahliae SP3 knock-out strain shows attenuated virulence and triggers less ROS production in cotton plants. To control the disease, we employ polyethyleneimine-coated MXene quantum dots (PEI-MQDs) that possess the ability to remove ROS. Cotton seedlings treated with PEI-MQDs are capable of maintaining ROS homeostasis with enhanced peroxidase, catalase, and glutathione peroxidase activities and exhibit improved tolerance to V. dahliae. These results suggest that V. dahliae trigger ROS production to promote infection and scavenging ROS is an effective way to manage this disease. This study reveals a virulence mechanism of V. dahliae and provides a means for V. dahliae resistance that benefits cotton production.