Introgression drives adaptation to the plateau environment in a subterranean rodent.

BACKGROUND: Introgression has repeatedly been shown to play an important role in the adaptation of species to extreme environments, yet how introgression enables rodents with specialized subterranean lifestyle to acclimatize to high altitudes is still unclear. Myospalacinae is a group of subterranean rodents, among which the high-altitude plateau zokors (Eospalax baileyi) and the low-altitude Gansu zokors (E. cansus) are sympatrically distributed in the grassland ecosystems of the Qinghai-Tibet Plateau (QTP). Together, they provide a model for the study of the role of introgression in the adaptation of low-altitude subterranean rodents to high altitudes. RESULTS: Applying low-coverage whole-genome resequencing and population genetics analyses, we identified evidence of adaptive introgression from plateau zokors into Gansu zokors, which likely facilitated the adaptation of the latter to the high-altitude environment of the QTP. We identified positively selected genes with functions related to energy metabolism, cardiovascular system development, calcium ion transport, and response to hypoxia which likely made critical contributions to adaptation to the plateau environment in both plateau zokors and high-altitude populations of Gansu zokors. CONCLUSIONS: Introgression of genes associated with hypoxia adaptation from plateau zokors may have played a role in the adaptation of Gansu zokors to the plateau environment. Our study provides new insights into the understanding of adaptive evolution of species on the QTP and the importance of introgression in the adaptation of species to high-altitude environments.

Single Molecular Nanomedicines Based on Macrocyclic Carrier-Drug Conjugates for Concentration-Independent Encapsulation and Precise Activation of Drugs.

Nanomedicines often rely on noncovalent self-assembly and encapsulation for drug loading and delivery. However, challenges such as reproducibility issues due to the multicomponent nature, off-target activation caused by premature drug release, and complex pharmacokinetics arising from assembly dissociation have hindered their clinical translation. In this study, we introduce an innovative design concept termed single molecular nanomedicine (SMNM) based on macrocyclic carrier-drug conjugates. Through the covalent linkage of two chemotherapy drugs to a hypoxia-cleavable macrocyclic carrier, azocalix[4]arene, we obtained two self-included complexes to serve as SMNMs. The intramolecular inclusion feature of the SMNMs has not only demonstrated comprehensive shielding and protection for the drugs but also effectively prevented off-target drug leakage, thereby significantly reducing their side effects and enhancing their antitumor therapeutic efficacy. Additionally, the attributes of being a single component and molecularly dispersed confer advantages such as ease of preparation and good reproducibility for SMNMs, which is desirable for clinical applications.

Naringenin ameliorates MASH fibrosis via regulating TAK1/MAPK/FoxO3a-mediated apoptosis in the activated hepatic stellate cells.

This study aims to explore the regulating effect and mechanism of naringenin (NGN) on the hepatic stellate cells (HSCs) apoptosis and its preventive effects on MASH fibrosis. C57BL/6 mice were subjected to either high-fat diet (HFD) plus carbon tetrachloride (CCl4) injection (HFD + CCl4) for 8 weeks to induce a MASH fibrosis model or bile duct ligation (BDL) to establish a liver fibrosis model, NGN was administered by gavage. LX2 cells were stimulated by oleic acid (OA) and lipopolysaccharide (LPS) (OA + LPS) to study the effects of NGN on activated hepatic stellate cell (HSC). Additionally, LO2 cells stimulated with OA + LPS were used to assess the protective effects of NGN on lipotoxicity of hepatocytes. Our in vivo results showed that NGN administration effectively inhibited mouse liver fibrosis in both of the MASH model and BDL model. The in vitro results indicate that NGN directly inhibited HSCs activation and promoted apoptosis of the activated HSCs, while it suppressed the apoptosis of LO2 cells induced by OA + LPS. The underlying mechanisms were mainly elucidated through the reduction of TAK1 phosphorylation, leading to the downregulation of p-JNK and p-ERK expression. This in turn, inhibited the phosphorylation of FoxO3a and promoted the nuclear localization of FoxO3a. Consequently, this may enhance the transcription of apoptosis-related genes, resulting in the apoptosis of activated HSCs. In conclusion, NGN ameliorates MASH fibrosis by enhancing apoptosis of the activated HSCs. The inhibitory effects of NGN on the TAK1/MAPK/FoxO3a pathway were demonstrated as its preventive mechanisms against MASH fibrosis.

High-Performance Photoinduced Tunneling Self-Driven Photodetector for Polarized Imaging and Polarization-Coded Optical Communication based on Broken-Gap ReSe2/SnSe2 van der Waals Heterojunction.

Novel 2D materials with low-symmetry structures exhibit great potential applications in developing monolithic polarization-sensitive photodetectors with small volume. However, owing to the fact that at least half of them presented a small anisotropic factor of ≈2, comprehensive performance of present polarization-sensitive photodetectors based on 2D materials is still lower than the practical application requirements. Herein, a self-driven photodetector with high polarization sensitivity using a broken-gap ReSe2/SnSe2 van der Waals heterojunction (vdWH) is demonstrated. Anisotropic ratio of the photocurrent (Imax/Imin) could reach 12.26 (635 nm, 179 mW cm-2). Furthermore, after a facile combination of the ReSe2/SnSe2 device with multilayer graphene (MLG), Imax/Imin of the MLG/ReSe2/SnSe2 can be further increased up to13.27, which is 4 times more than that of pristine ReSe2 photodetector (3.1) and other 2D material photodetectors even at a bias voltage. Additionally, benefitting from the synergistic effect of unilateral depletion and photoinduced tunneling mechanism, the MLG/ReSe2/SnSe2 device exhibits a fast response speed (752/928 µs) and an ultrahigh light on/off ratio (105). More importantly, MLG/ReSe2/SnSe2 device exhibits excellent potential applications in polarized imaging and polarization-coded optical communication with quaternary logic state without any power supply. This work provides a novel feasible avenue for constructing next-generation smart polarization-sensitive photodetector with low energy consumption.

Metagenomic next-generation sequencing in detecting pathogens in pediatric oncology patients with suspected bloodstream infections.

BACKGROUND: Studies on mNGS application in pediatric oncology patients, who are at high risk of infection, are quite limited. METHODS: From March 2020 to June 2022, a total of 224 blood samples from 195 pediatric oncology patients who were suspected as bloodstream infections were enrolled in this study. Their clinical and laboratory data were retrospectively reviewed, and the diagnostic performance of mNGS was assessed. RESULTS: Compared to the reference tests, mNGS showed significantly higher sensitivity (89.8% vs 32.5%, P < 0.001) and clinical agreement (76.3% vs 51.3%, P < 0.001) in detecting potential pathogens and distinguishing BSI from non-BSI. Especially, mNGS had an outstanding performance for virus detection, contributing to 100% clinical diagnosed virus. Samples from patients with neutropenia showed higher incidence of bacterial infections (P = 0.035). The most identified bacteria were Escherichia coli, and the overall infections by gram-negative bacteria were significantly more prevalent than those by gram-positive ones (90% vs 10%, P < 0.001). Overall, mNGS had an impact on the antimicrobial regimens' usage in 54.3% of the samples in this study. CONCLUSIONS: mNGS has the advantage of rapid and effective pathogen diagnosis in pediatric oncology patients with suspected BSI, especially for virus. IMPACT: Compared with reference tests, mNGS showed significantly higher sensitivity and clinical agreement in detecting potential pathogens and distinguishing bloodstream infections (BSI) from non-BSI. mNGS is particularly prominent in clinical diagnosed virus detection. The incidence of bacterial infection was higher in patients with neutropenia, and the overall infection rate of Gram-negative bacteria was significantly higher than that of Gram-positive bacteria. mNGS affects the antimicrobial regimens' usage in more than half of patients.

Relationship between chronic disease resource utilization and quality of life in coronary heart disease patients: A latent profile analysis.

AIMS: This study aimed to identify different profiles of chronic disease resource utilization among patients with coronary heart disease in Tibet and explore the relationship between these profiles and quality of life. DESIGN: A cross-sectional study. METHODS: Patients with coronary heart disease who were treated in a tertiary hospital in Tibet and its cooperative points from January 2021 to July 2021 were selected as the study participants. All participants completed a general information questionnaire, the Chronic Disease Resource Utilization Questionnaire (CIRS) and the Health Status Survey Short Form (SF-36). Chronic disease resource utilization was profiled, and its relationship to quality of life was explored using hierarchical linear regression. RESULTS: A total of 382 patients were enrolled in this study. Regarding chronic disease resource utilization, the participants were divided into three latent profiles: 'Poor utilization group' (n = 151), 'Effective utilization group' (n = 155) and 'Full utilization group' (n = 76). Different profiles of chronic disease resource utilization of patients were significantly associated with quality of life (R2 = .126, p < .001). CONCLUSION: Healthcare providers should identify patients with different profiles, define their utilization features of chronic disease resources and adopt targeted interventions to guide them in acquiring enough disease support resources to improve their quality of life. IMPLICATION: Understanding different resources using preferences of coronary heart disease patients can help healthcare providers and related sectors to provide other supports based on different profiles of patients, thus enhancing their quality of life. REPORTING METHOD: The study followed the STROBE guideline. NO PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public involvement in the design of the study.

ESE-YOLOv8: A Novel Object Detection Algorithm for Safety Belt Detection during Working at Heights.

To address the challenges associated with supervising workers who wear safety belts while working at heights, this study proposes a solution involving the utilization of an object detection model to replace manual supervision. A novel object detection model, named ESE-YOLOv8, is introduced. The integration of the Efficient Multi-Scale Attention (EMA) mechanism within this model enhances information entropy through cross-channel interaction and encodes spatial information into the channels, thereby enabling the model to obtain rich and significant information during feature extraction. By employing GSConv to reconstruct the neck into a slim-neck configuration, the computational load of the neck is reduced without the loss of information entropy, allowing the attention mechanism to function more effectively, thereby improving accuracy. During the model training phase, a regression loss function named the Efficient Intersection over Union (EIoU) is employed to further refine the model's object localization capabilities. Experimental results demonstrate that the ESE-YOLOv8 model achieves an average precision of 92.7% at an IoU threshold of 50% and an average precision of 75.7% within the IoU threshold range of 50% to 95%. These results surpass the performance of the baseline model, the widely utilized YOLOv5 and demonstrate competitiveness among state-of-the-art models. Ablation experiments further confirm the effectiveness of the model's enhancements.

Sporogenesis, gametophyte development and embryogenesis in Glehnia littoralis.

BACKGROUND: Glehnia littoralis is an economic herb with both medicinal and edible uses. It also has important ecological value and special phylogenetic status as it is a monotypic genus species distributing around beach. Little information on its reproductive biology has been reported so far, which has hindered conservation and application of this species. In this study, we observed morphological changes from buds emergence to seeds formation and internal changes during sporogenesis, gametophyte development and embryo and endosperm development of G. littoralis using paraffin-embedded-sectioning and stereo microscope. RESULTS: The results showed that the stages of internal development events of G. littoralis corresponded to obvious external morphological changes, most of developmental features were consistent with other Apiaceae species. The development of male and female gametophytes was not synchronized in the same flower, however, exhibited temporal overlap. From mid-late April to mid-May, the anther primordial and ovule primordial developed into the trinucleate pollen grain and eight-nuclear embryo sac, respectively. From late-May to mid-July, the zygote developed into mature embryo. In addition, some defects in gynoecium or ovule development and abnormal embryo and endosperm development were found. We induced that the possible causes of abortion in G. littoralis were as follows: nutrient limitation, poor pollination and fertilization, and bad weather. CONCLUSIONS: This study revealed the whole process and morphological characteristics of the development of reproductive organ in G. littoralis, which not only provided important data for the study of systematic and conservation biology, but also provided a theoretical basis for cross breeding.

A New Risk Score for Predicting Postoperative Mortality in Suspected Heart Failure Patients Undergoing Valvular Surgery.

Background: Heart failure (HF) is one of the most important indications of the severity of valvular heart disease (VHD). VHD with HF is frequently associated with a higher surgical risk. Our study sought to develop a risk score model to predict the postoperative mortality of suspected HF patients after valvular surgery. Methods: Between January 2016 and December 2018, all consecutive adult patients suspected of HF and undergoing valvular surgery in the Chinese Cardiac Surgery Registry (CCSR) database were included. Finally, 14,645 patients (55.39 ± 11.6 years, 43.5% female) were identified for analysis. As a training group for model derivation, we used patients who had surgery between January 2016 and May 2018 (11,292 in total). To validate the model, patients who underwent surgery between June 2018 and December 2018 (a total of 3353 patients) were included as a testing group. In training group, we constructed and validated a scoring system to predict postoperative mortality using multivariable logistic regression and bootstrapping method (1000 re-samples). We validated the scoring model in the testing group. Brier score and calibration curves using bootstrapping with 1000 re-samples were used to evaluate the calibration. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the discrimination. The results were also compared to EuroSCORE II. Results: The final score ranged from 0 to 19 points and involved 9 predictors: age ≥ 60 years; New York Heart Association Class (NYHA) IV; left ventricular ejection fraction (LVEF) < 35%; estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m 2 ; preoperative dialysis; Left main artery stenosis; non-elective surgery; cardiopulmonary bypass (CPB) time > 200 minutes and perioperative transfusion. In training group, observed and predicted postoperative mortality rates increased from 0% to 45.5% and from 0.8% to 50.3%, respectively, as the score increased from 0 up to ≥ 10 points. The scoring model's Brier scores in the training and testing groups were 0.0279 and 0.0318, respectively. The area under the curve (AUC) values of the scoring model in both the training and testing groups were 0.776, which was significantly higher than EuroSCORE II in both the training (AUC = 0.721, Delong test, p < 0.001) and testing (AUC = 0.669, Delong test, p < 0.001) groups. Conclusions: The new risk score is an effective and concise tool that could accurately predict postoperative mortality rates in suspected HF patients after valve surgery.

Development of an antibody-ligand fusion protein scFvCD16A-sc4-1BBL in Komagataella phaffii with stimulatory activity for Natural Killer cells.

BACKGROUND: Natural killer (NK) cell-based immunotherapies have demonstrated substantial potential for the treatment of hematologic malignancies. However, its application is limited due to the difficulty in the production of a large number of NK cells in vitro and the insufficient therapeutic efficacy against solid tumors in vivo. Engineered antibodies or fusion proteins targeting activating receptors and costimulatory molecules of NK cells have been developed to encounter these problems. They are mostly produced in mammalian cells with high cost and long processing times. Yeast systems, such as Komagataella phaffii, present a convenient manipulation of microbial systems with the key advantages of improved folding machinery and low cost. RESULTS: In this study, we designed an antibody fusion protein scFvCD16A-sc4-1BBL, composed of the single chain variant fragment (scFv) of anti-CD16A antibody and the three extracellular domains (ECDs) of human 4-1BBL in a single-chain format (sc) with the GS linker, aiming to boost NK cell proliferation and activation. This protein complex was produced in the K. phaffii X33 system and purified by affinity chromatography and size exclusion chromatography. The scFvCD16A-sc4-1BBL complex showed comparable binding abilities to its two targets human CD16A and 4-1BB as its two parental moieties (scFvCD16A and monomer ECD (mn)4-1BBL). scFvCD16A-sc4-1BBL specifically stimulated the expansion of peripheral blood mononuclear cell (PBMC)-derived NK cells in vitro. Furthermore, in the ovarian cancer xenograft mouse model, adoptive NK cell infusion combined with intraperitoneal (i.p) injection of scFvCD16A-sc4-1BBL further reduced the tumor burden and prolonged the survival time of mice. CONCLUSION: Our studies demonstrate the feasibility of the expression of the antibody fusion protein scFvCD16A-sc4-1BBL in K. phaffii with favourable properties. scFvCD16A-sc4-1BBL stimulates PBMC-derived NK cell expansion in vitro and improves the antitumor activity of adoptively transferred NK cells in a murine model of ovarian cancer and may serve as a synergistic drug for NK immunotherapy in future research and applications.

Solvent-Free Grinding Synthesis of Hybrid Copper Halides for White Light Emission.

Lead-free metal halides (LMHs) have recently attracted numerous attention in solid-state lighting due to their unique structures and outstanding optoelectronic properties. However, conventional preparation processes with the utilization of toxic organic solvents and high temperatures seem to impede commercial applications of LMHs. In this work, we successfully synthesize Cu+-based metal halides (TMA)3Cu2Br5-xClx (TMA: tetramethylammonium) with high photoluminescence quantum yields (PLQYs) via a solvent-free mechanical grinding method. By changing the ratio of halide ions (Cl- and Br-) in precursors, the emission wavelength of the prepared (TMA)3Cu2Br5-xClx can be tuned from 535 to 587 nm, which are employed as emitters in the fabrication of white-light-emitting diodes (WLEDs). The achieved WLEDs exhibit a high color rendering index value of 84 and standard Commission Internationale de l'Éclairage (CIE) coordinates of (0.324, 0.333). This feasible and solvent-free preparation strategy not only promotes the mass production of LMHs but also highlights the promising potential for efficient solid-state illumination.

Complete chloroplast genome and phylogenetic analysis of Anemone shikokiana.

BACKGROUND: Anemone shikokiana (Makino) Makino, disjunctly distributed in Shandong Peninsula of China and Shikoku Island of Japan, is a rare and endangered species. To provide genetic information and understand its phylogeny, we conducted research on the chloroplast (cp) genome of A. shikokiana. METHODS AND RESULTS: The complete cp genome sequence of A. shikokiana was constructed in this study. The results showed that the cp genome of A. shikokiana has a typical quadripartite cyclic with a total length of 159,286 bp. In total, 111 unique genes were identified, including 78 protein-coding genes, 29 tRNA-coding genes and 4 rRNA-coding genes. A total of 37 long repeat sequences and 67 microsatellites were found in this cp genome. The cp genome of A. shikokiana was compared with eleven other Anemone cp genomes available from the Genbank database. We found some variations among the different genomes, especially in the LSC and SSC regions, and identified some regions as potential molecular markers such as ycf1, ndhE, ndhD, ndhF-trnL, ndhA and ndhF. The results of phylogenetic analysis suggested that A. narcissiflora was the closest relative of A. shikokiana. CONCLUSIONS: The results filled the gap of cp genome sequence information of A. shikokiana, laying the foundation to explore the evolutionary relationships of A. shikokiana in future studies. It provided a valuable genetic resource for the molecular identification and phylogenetic study of Anemone.

Enhanced transverse magneto-optical Kerr effect using ferromagnetic metal perforated with nanopore arrays.

Enhancement of transverse magneto-optical Kerr effects (T-MOKEs) based on surface plasmon resonance has attracted wide attention because of their high sensing performance. Most studies, however, mainly focus on prism-based magnetoplasmonic structures or architectures that incorporate a noble metal lattice and ferromagnetic layer, hindering device fabrication, miniaturization, and integration into a microfluidic sensing configuration. Herein, we propose a single Co6Ag94 ferromagnetic-metal layer perforated with a square nanopore array system with a pronounced T-MOKE magnitude 51 times higher than that of a smooth film, and with potential to detect gaseous analytes. The proposed system is sufficient to detect gaseous media for early environmental monitoring and enables an accessible pathway for magneto-optical sensor design.

'I'm still young it doesn't matter' - A qualitative study on the neglect of prodromal myocardial infarction symptoms among young- and middle-aged adults.

AIM: To explore why young- and middle-aged adults ignore prodromal myocardial infarction symptoms from a life course and sociocultural perspective. DESIGN: A qualitative descriptive study. METHODS: We applied purposeful sampling to recruit participants from a tertiary hospital in Guangzhou from July to November 2021. Face-to-face interviews were performed. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis methods. RESULTS: Twenty-four young- and middle-aged adults diagnosed with acute myocardial infarction participated in this study. Analysis revealed three main themes: I'm still young, it will not happen to me; to be somebody and different roles, multiple pressures. Age-related self-confidence led to inappropriate perceptions and responses to prodromal symptoms among young- and middle-aged adults. These individuals strived to align their behaviours and attention with social expectations and self-expectations, underestimating the importance of perceiving the warning signs of acute myocardial infarction and seeking medical treatment. Pressure from social roles also prevented them from paying enough attention to prodromal symptoms. CONCLUSION: Targeted social support, public education and technologies should be provided to these individuals since they are pillars of the family and society. We also highlight how nurses can function these strategies appropriately. IMPACTS: This study contributes to a better understanding of the neglect of prodromal symptoms among young- and middle-aged adults. Its results enhance our understanding of the perception of and coping with prodromal symptoms among this population, which will help avoid the burden caused by acute myocardial infarction. PATIENT OR PUBLIC CONTRIBUTION: The patients involved in our study shared their experiences and insights to provide new perspectives regarding the neglect of prodromal myocardial infarction symptoms among young- and middle-aged adults.

Familiarity of teaching skills among general practitioners transfer training trainers in China: a cross-sectional survey.

BACKGROUND: The insufficient number of general practitioners (GPs) is a major challenge facing China's healthcare system. The purpose of the GP transfer training programme was to provide training for experienced doctors to transition to general practice. However, research on the competencies of GP transfer training trainers in teaching skills in China is limited. This cross-sectional study aimed to examine the baseline familiarity with teaching skills among Chinese GP transfer training trainers. METHODS: An online survey was conducted among trainers who participated in the 2021 Sichuan Province General Practice Training Trainer Program. The survey collected data on participants' characteristics and familiarity with 20 skills in three essential teaching knowledge areas: the core functions of primary care (five questions), preparation for lesson plan (four questions), and teaching methods (11 questions). RESULTS: In total, 305 participants completed the survey. Familiarity rates were generally low across all three essential teaching knowledge areas. No significant differences were observed in familiarity rates between the tertiary and secondary hospitals. CONCLUSION: This study revealed gaps in the teaching skills of GP transfer training trainers in China. These results suggest the necessity for targeted training programs to enhance the teaching skills and competencies of trainers.

User Pairing for Delay-Limited NOMA-Based Satellite Networks with Deep Reinforcement Learning.

In this paper, we investigate a user pairing problem in power domain non-orthogonal multiple access (NOMA) scheme-aided satellite networks. In the considered scenario, different satellite applications are assumed with various delay quality-of-service (QoS) requirements, and the concept of effective capacity is employed to characterize the effect of delay QoS limitations on achieved performance. Based on this, our objective was to select users to form a NOMA user pair and utilize resource efficiently. To this end, a power allocation coefficient was firstly obtained by ensuring that the achieved capacity of users with sensitive delay QoS requirements was not less than that achieved with an orthogonal multiple access (OMA) scheme. Then, considering that user selection in a delay-limited NOMA-based satellite network is intractable and non-convex, a deep reinforcement learning (DRL) algorithm was employed for dynamic user selection. Specifically, channel conditions and delay QoS requirements of users were carefully selected as state, and a DRL algorithm was used to search for the optimal user who could achieve the maximum performance with the power allocation factor, to pair with the delay QoS-sensitive user to form a NOMA user pair for each state. Simulation results are provided to demonstrate that the proposed DRL-based user selection scheme can output the optimal action in each time slot and, thus, provide superior performance than that achieved with a random selection strategy and OMA scheme.

Table Tennis Track Detection Based on Temporal Feature Multiplexing Network.

Recording the trajectory of table tennis balls in real-time enables the analysis of the opponent's attacking characteristics and weaknesses. The current analysis of the ball paths mainly relied on human viewing, which lacked certain theoretical data support. In order to solve the problem of the lack of objective data analysis in the research of table tennis competition, a target detection algorithm-based table tennis trajectory extraction network was proposed to record the trajectory of the table tennis movement in video. The network improved the feature reuse rate in order to achieve a lightweight network and enhance the detection accuracy. The core of the network was the "feature store & return" module, which could store the output of the current network layer and pass the features to the input of the network layer at the next moment to achieve efficient reuse of the features. In this module, the Transformer model was used to secondarily process the features, build the global association information, and enhance the feature richness of the feature map. According to the designed experiments, the detection accuracy of the network was 96.8% for table tennis and 89.1% for target localization. Moreover, the parameter size of the model was only 7.68 MB, and the detection frame rate could reach 634.19 FPS using the hardware for the tests. In summary, the network designed in this paper has the characteristics of both lightweight and high precision in table tennis detection, and the performance of the proposed model significantly outperforms that of the existing models.

Potential Role of Anti-Müllerian Hormone in Regulating Seasonal Reproduction in Animals: The Example of Males.

Seasonal reproduction is a survival strategy by which animals adapt to environmental changes to improve their fitness. Males are often characterized by a significantly reduced testicular volume, indicating that they are in an immature state. Although many hormones, including gonadotropins, have played a role in testicular development and spermatogenesis, research on other hormones is insufficient. The anti-Müllerian hormone (AMH), which is a hormone responsible for inducing the regression of Müllerian ducts involved in male sex differentiation, was discovered in 1953. Disorders in AMH secretion are the main biomarkers of gonadal dysplasia, indicating that it may play a crucial role in reproduction regulation. A recent study has found that the AMH protein is expressed at a high level during the non-breeding period of seasonal reproduction in animals, implying that it may play a role in restricting breeding activities. In this review, we summarize the research progress on the AMH gene expression, regulatory factors of the gene's expression, and its role in reproductive regulation. Using males as an example, we combined testicular regression and the regulatory pathway of seasonal reproduction and attempted to identify the potential relationship between AMH and seasonal reproduction, to broaden the physiological function of AMH in reproductive suppression, and to provide new ideas for understanding the regulatory pathway of seasonal reproduction.

Reproductive Suppression Caused by Spermatogenic Arrest: Transcriptomic Evidence from a Non-Social Animal.

Reproductive suppression is an adaptive strategy in animal reproduction. The mechanism of reproductive suppression has been studied in social animals, providing an essential basis for understanding the maintenance and development of population stability. However, little is known about it in solitary animals. The plateau zokor is a dominant, subterranean, solitary rodent in the Qinghai-Tibet Plateau. However, the mechanism of reproductive suppression in this animal is unknown. We perform morphological, hormonal, and transcriptomic assays on the testes of male plateau zokors in breeders, in non-breeders, and in the non-breeding season. We found that the testes of non-breeders are smaller in weight and have lower serum testosterone levels than those of breeders, and the mRNA expression levels of the anti-Müllerian hormone (AMH) and its transcription factors are significantly higher in non-breeder testes. Genes related to spermatogenesis are significantly downregulated in both meiotic and post-meiotic stages in non-breeders. Genes related to the meiotic cell cycle, spermatogenesis, flagellated sperm motility, fertilization, and sperm capacitation are significantly downregulated in non-breeders. Our data suggest that high levels of AMH may lead to low levels of testosterone, resulting in delayed testicular development, and physiological reproductive suppression in plateau zokor. This study enriches our understanding of reproductive suppression in solitary mammals and provides a basis for the optimization of managing this species.

An Antitumor Dual-Responsive Host-Guest Supramolecular Polymer Based on Hypoxia-Cleavable Azocalix[4]arene.

The exploitation of specific guests which can respond to external stimuli is the main approach for the construction of stimuli-responsive supramolecular polymers (SPs) based on host-guest interactions. Most functional guests, however, fail to manifest stimuli-responses. Herein, a hypoxia-responsive dimeric azocalixarene (D-SAC4A) with outstanding hosting properties was used as the macrocyclic building block for the preparation of host stimuli-responsive SPs. Since azocalixarenes can also be compatible with stimuli-responsive guests, an antitumor drug, camptothecin (CPT), was chosen and linked via a disulfide-containing linker to afford a glutathione (GSH)-responsive ditropic guest (D-CPT). A unique dual-responsive SP was obtained by 1 : 1 mixing of D-SAC4A and D-CPT in water, which further assembled into SP nanoparticles (DSPNs). DSPNs displayed outstanding stability against dilution and biological interferants, as well as precise CPT-release under GSH and hypoxia conditions. In vitro and in vivo experiments demonstrated the good biosafety and tumor-suppressive effects of DSPNs.