Physiological and transcriptome level responses of Microcystis aeruginosa and M. viridis to environmental concentrations of triclosan.

The toxicity of triclosan (TCS) to various aquatic organisms has been demonstrated at environmental concentrations. However, the effects and mechanisms of TCS on toxic cyanobacteria remains largely unexplored. This study investigated the physiological and molecular variations in two representative toxic Microcystis species (M. aeruginosa and M. viridis) under exposure to TCS for 12 d. Our findings demonstrated that the median effective concentration (EC50) of TCS for both Microcystis species were close to the levels detected in the environment (M. aeruginosa: 9.62 µg L-1; M. viridis: 27.56 µg L-1). An increased level of reactive oxygen species (ROS) was observed in Microcystis, resulting in oxidative damage when exposed to TCS at concentrations ranging from 10 µg L-1 to 50 µg L-1. The photosynthetic activity of Microcystis had a certain degree of recovery capability at low concentrations of TCS. Compared to M. aeruginosa, the higher recovery capability of the photosynthetic system in M. viridis would be mainly attributed to the increased ability for PSII repair and phycobilisome synthesis. Additionally, the synthesis of microcystins in the two species and the release rate in M. viridis significantly increased under 10-50 µg L-1 TCS. At the molecular level, exposure to TCS at EC50 for 12 d induced the dysregulation of genes associated with photosynthesis and antioxidant system. The upregulation of genes associated with microcystin synthesis and nitrogen metabolism further increased the potential risk of microcystin release. Our results revealed the aquatic toxicity and secondary ecological risks of TCS at environmental concentrations, and provided theoretical data with practical reference value for TCS monitoring.

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.

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.

Classification and Treatment Strategies of Tibial Tubercle Fractures in Adults.

OBJECTIVES: Tibial tubercle is a crucial player in maintaining the structural integrity and functional stability of the knee joint. Currently, there is no standardized protocol for the classification and treatment of tibial tubercle fractures in adults. This study analyzed the incidence and treatment strategies of tibial tubercle fractures in adults according to the four-column and nine-segment classification system. METHODS: Data of patients with proximal tibial fractures involving tibial tubercle fractures who were treated at our hospital from August 2007 to March 2023 were retrospectively reviewed. The fractures were classified using the AO/OTA classification and four-column and nine-segment classification systems, and the treatment protocol (surgically treated or conservatively treated) was recorded. The number and distribution proportion of patients were counted. A two-sided t-test was conducted to determine the significance of differences between the gender and sides. RESULTS: In total, 169 tibial tubercle fractures were found in 1484 proximal tibial fractures. According to the AO/OTA classification, seven of the 169 patients, (4.1%) were type A, 36 patients (21.3%) were type B, and 126 patients (74.6%) were type C. According to the four-column and nine-segment classification, type 1 cleavage without free fragments was the most common type of fracture (93/169, 55.0%), followed by type 2 dissociative segmental fragments (48/169, 28.4%) and type 3 comminuted fractures (28/169, 16.6%). Overall, 139 of the 169 proximal tibial fractures with tuberosity involvement were treated surgically. Among them, additional fixation of the tubercle fragment was performed in 52 fractures. CONCLUSION: The incidence of tibial tubercle fractures involved in proximal tibial fractures was approximately 11.4% (169/1484) in adults, and approximately one-third of the tubercle bone fragment required additional fixation (30.8%, 52/169). The injury types in the four-column and nine-segment classifications are helpful for accurately judging and making treatment-related decisions for tibial tubercle fractures.

Evaluation of the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer: A study protocol of prospective single-center, randomized controlled and open label clinical trial (RNPLS-01).

Objective: Ramucirumab is a VEGFR2 antagonist. The aim of this trial is to evaluate the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer. Methods: and analysis: This study is a prospective single-center, randomized controlled and open label clinical study, enrolling a total of 140 patients with advanced gastric cancer distributed across two distinct cohorts (Cohort A n = 70; Cohort B n = 70). The central focus of the study lies in evaluating the pathological complete response (pCR) of the cancer post-neoadjuvant or conversion therapy. Secondary endpoints encompass the assessment of the R0 resection rate subsequent to the aforementioned therapies, the occurrence of adverse events (AE), progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the total response rate and its duration, the disease control rate (DCR), and the duration of overall response (DOR). Ethics: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Air force Military Medical University (KY20232220-F-1). Trial registration: This trial has been registered at the ClinicalTrials.gov: NCT06169410 (registration date: December 5, 2023).

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.

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.

Research on accurate pipetting complementation model for high-throughput molecular detection platform.

The incidence of infectious diseases has risen in recent years, leading to a significant surge in the demand for medical molecular detection. High-throughput molecular detection platforms play a crucial role in facilitating rapid and efficient molecular detection. Among the various techniques employed in high-throughput molecular detection, microliquid transfer stands out as one of the most frequently utilized methods. However, ensuring the accuracy of liquid transfer poses a challenge due to variations in the physical and chemical properties of different samples and reagents. In this study, a pipetting complementation model was developed specifically for the serum, paraffin oil, and throat swabs. The aim was to enhance the transfer accuracy of diverse liquids in the context of high-throughput molecular detection, ultimately ensuring detection reliability and stability. The experimental findings revealed notable improvements in pipetting accuracy after compensating for the three liquids. In particular, the pipetting error rates decreased by 52.5, 96, and 71.4% for serum, paraffin oil, and throat swabs, respectively. These results underscore the model's effectiveness in providing reliable support for the precise transfer of liquids on the high-throughput molecular detection platform.

Multipathway Regulation for Targeted Atherosclerosis Therapy Using Anti-miR-33-Loaded DNA Origami.

Given the multifactorial pathogenesis of atherosclerosis (AS), a chronic inflammatory disease, combination therapy arises as a compelling approach to effectively address the complex interplay of pathogenic mechanisms for a more desired treatment outcome. Here, we present cRGD/ASOtDON, a nanoformulation based on a self-assembled DNA origami nanostructure for the targeted combination therapy of AS. cRGD/ASOtDON targets αvß3 integrin receptors overexpressed on pro-inflammatory macrophages and activated endothelial cells in atherosclerotic lesions, alleviates the oxidative stress induced by extracellular and endogenous reactive oxygen species, facilitates the polarization of pro-inflammatory macrophages toward the anti-inflammatory M2 phenotype, and inhibits foam cell formation by promoting cholesterol efflux from macrophages by downregulating miR-33. The antiatherosclerotic efficacy and safety profile of cRGD/ASOtDON, as well as its mechanism of action, were validated in an AS mouse model. cRGD/ASOtDON treatment reversed AS progression and restored normal morphology and tissue homeostasis of the diseased artery. Compared to probucol, a clinical antiatherosclerotic drug with a similar mechanism of action, cRGD/ASOtDON enabled the desired therapeutic outcome at a notably lower dosage. This study demonstrates the benefits of targeted combination therapy in AS management and the potential of self-assembled DNA nanoformulations in addressing multifactorial inflammatory conditions.

Targeting blood brain barrier-Remote ischemic conditioning alleviates cognitive impairment in female APP/PS1 rats.

AIMS: Alzheimer's disease (AD) is a significant global health concern, and it is crucial that we find effective methods to prevent or slow down AD progression. Recent studies have highlighted the essential role of blood vessels in clearing Aß, a protein that contributes to AD. Scientists are exploring blood biomarkers as a potential tool for future AD diagnosis. One promising method that may help prevent AD is remote ischemic conditioning (RIC). RIC involves using sub-lethal ischemic-reperfusion cycles on limbs. However, a comprehensive understanding of how RIC can prevent AD and its long-term effectiveness is still lacking. Further research is essential to fully comprehend the potential benefits of RIC in preventing AD. METHODS: Female wild-type (WT) and APP/PS1 transgenic rats, aged 12 months, underwent ovariectomy and were subsequently assigned to WT, APP/PS1, and APP/PS1 + RIC groups. RIC was conducted five times a week for 4 weeks. The rats' depressive and cognitive behaviors were evaluated using force swimming, open-field tests, novel objective recognition, elevated plus maze, and Barnes maze tests. Evaluation of the neurovascular unit (NVU), synapses, vasculature, astrocytes, and microglia was conducted using immunofluorescence staining (IF), Western blot (WB), and transmission electron microscopy (TEM). Additionally, the cerebro-vasculature was examined using micro-CT, and cerebral blood flow (CBF) was measured using Speckle Doppler. Blood-brain barrier (BBB) permeability was determined by measuring the Evans blue leakage. Finally, Aß levels in the rat frontal cortex were measured using WB, ELISA, or IF staining. RESULTS: RIC enhanced memory-related protein expression and rescued depressive-like behavior and cognitive decline in APP/PS1 transgenic rats. Additionally, the intervention protected NVU in the rat frontal cortex, as evidenced by (1) increased expression of TJ (tight junction) proteins, pericyte marker PDGFRß, and glucose transporter 1 (GLUT1), as well as decreased VCAM1; (2) mitigation of ultrastructure impairment in neuron, cerebral vascular, and astrocyte; (3) upregulation of A2 astrocyte phenotype markers and downregulation of A1 phenotype markers, indicating a shift toward a healthier phenotype. Correspondingly, RIC intervention alleviated neuroinflammation, as evidenced by the decreased Iba1 level, a microglia marker. Meanwhile, RIC intervention elevated CBF in frontal cortex of the rats. Notably, RIC intervention effectively suppressed Aß toxicity, as demonstrated by the enhancement of α-secretase and attenuation of ß-secretase (BACE1) and γ- secretase and Aß1-42 and Aß1-40 levels as well. CONCLUSION: Chronic RIC intervention exerts vascular and neuroprotective roles, suggesting that RIC could be a promising therapeutic strategy targeting the BBB and NVU during AD development.

Lysosomal destabilization: A missing link between pathological calcification and osteoarthritis.

Calcification of cartilage by hydroxyapatite is a hallmark of osteoarthritis and its deposition strongly correlates with the severity of osteoarthritis. However, no effective strategies are available to date on the prevention of hydroxyapatite deposition within the osteoarthritic cartilage and its role in the pathogenesis of this degenerative condition is still controversial. Therefore, the present work aims at uncovering the pathogenic mechanism of intra-cartilaginous hydroxyapatite in osteoarthritis and developing feasible strategies to counter its detrimental effects. With the use of in vitro and in vivo models of osteoarthritis, hydroxyapatite crystallites deposited in the cartilage are found to be phagocytized by resident chondrocytes and processed by the lysosomes of those cells. This results in lysosomal membrane permeabilization (LMP) and release of cathepsin B (CTSB) into the cytosol. The cytosolic CTSB, in turn, activates NOD-like receptor protein-3 (NLRP3) inflammasomes and subsequently instigates chondrocyte pyroptosis. Inhibition of LMP and CTSB in vivo are effective in managing the progression of osteoarthritis. The present work provides a conceptual therapeutic solution for the prevention of osteoarthritis via alleviation of lysosomal destabilization.

A screening for optimal selenium enrichment additives for selenium-enriched fish production: Application of a HPLC-ICP-MS method.

The production of selenium-enriched fish contributes to alleviating selenium deficiency for humans. In this study, selenium nanoparticles (SeNPs) comparable in bioavailability to selenomethionine (SeMet), increased SeMet content in O. macrolepis (Onychostoma macrolepis) muscle. Additionally, dietary SeNPs significantly enhanced selenocysteine (SeCys2) and methylselenocysteine (MeSeCys) levels in O. macrolepis muscle. The effect of SeNPs on selenium speciation in grass carp muscle was consistent with O. macrolepis results. SeCys2 and MeSeCys showed antioxidant capacity in HEK293T cells, indicating enhanced health benefits of Se-enriched fish produced using SeNPs. Furthermore, the addition of 0.3 mg/kg SeNPs significantly improved the flesh quality of O. macrolepis by reducing the content of crude fat and heavy metals, as well as increasing the levels of crude protein, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and the ratio of n-3/n-6 polyunsaturated fatty acids (PUFAs). Therefore, selenium-enriched fish produced from SeNPs is a good source for improving human dietary selenium intake.

Biomimetic Self-Maturation Mineralization System for Enamel Repair.

Enamel repair is crucial for restoring tooth function and halting dental caries. However, contemporary research often overlooks the retention of organic residues within the repair layer, which hinders the growth of dense crystals and compromises the properties of the repaired enamel. During the maturation of natural enamel, the organic matrix undergoes enzymatic processing to facilitate further crystal growth, resulting in a highly mineralized tissue. Inspired by this process, a biomimetic self-maturation mineralization system is developed, comprising ribonucleic acid-stabilized amorphous calcium phosphate (RNA-ACP) and ribonuclease (RNase). The RNA-ACP induces initial mineralization in the form of epitaxial crystal growth, while the RNase present in saliva automatically triggers a biomimetic self-maturation process. The mechanistic study further indicates that RNA degradation prompts conformational rearrangement of the RNA-ACP, effectively excluding the organic matter introduced earlier. This exclusion process promotes lateral crystal growth, resulting in the generation of denser enamel-like apatite crystals that are devoid of organic residues. This strategy of eliminating organic residues from enamel crystals enhances the mechanical and physiochemical properties of the repaired enamel. The present study introduces a conceptual biomimetic mineralization strategy for effective enamel repair in clinical practice and offers potential insights into the mechanisms of biomineral formation.

Association of residential greenness, air pollution with adverse birth outcomes: Results from 61,762 mother­neonatal pairs in project ELEFANT (2011-2021).

BACKGROUND: Emerging evidence has demonstrated the benefits of greenness exposure on human health, while conflicts remain unsolved in issue of adverse birth outcomes. METHODS: Utilizing data from project ELEFANT spanning the years 2011 to 2021, we assessed residential greenness using the NDVI from MODIS data and residential PM2.5 exposure level from CHAP data. Our primary concerns were PTD, LBW, LGA, and SGA. Cox proportional hazard regression model was used to examine the association of residential greenness and air pollution exposure with risk of adverse birth outcomes. We performed mediation and modification effect analyses between greenness and air pollutant. RESULTS: We identified 61,762 mother­neonatal pairs in final analysis. For per 10 µg/m3 increase in PM2.5 concentration during entire pregnancy was associated with 19.8 % and 20.7 % increased risk of PTD and LGA. In contrast, we identified that an 0.1 unit increment in NDVI were associated with 24 %, 43 %, 26.5 %, and 39.5 % lower risk for PTD, LBW, LGA, and SGA, respectively. According to mediation analysis, NDVI mediated 7.70 % and 7.89 % of the associations between PM2.5 and PTD and LGA. Residential greenness could reduce the risk of PTD among mothers under 35 years old, living in rural areas, primigravidae and primiparity.. CONCLUSIONS: In summary, our results highlighted the potential of residential greenness to mitigate the risk of adverse birth outcomes, while also pointing to the adverse impact of PM2.5 on increased risk of multiple adverse birth outcomes (PTD and LGA). The significant mediation effect of NDVI emphasizes its potential as an important protective factor of PM2.5 exposure. Additionally, the identification of susceptible subgroups can inform targeted interventions to reduce adverse birth outcomes related to air pollution and lack of green spaces. Further research and understanding of these associations can contribute to better public health strategies aimed at promoting healthier pregnancies and birth outcomes.

Assessing the suitability and dynamics of three medicinal Sambucus species in China under current and future climate scenarios.

Climate change exerts profound influences on the ecological environments on a global scale, leading to habitat destruction and altering distribution patterns for numerous plant species. Traditional Chinese medicinal plants, such as those belonging to the Sambucus genus, have been extensively utilized for several centuries to treat fractures, rheumatism, and inflammation. However, our understanding of their geographic distribution and climatic adaptation within China still needs to be improved. In this study, we screened the optimal predictive model (random forest model) to predict the potential suitable distribution of three Sambucus species (Sambucus adnata, Sambucus javanica, and Sambucus williamsii) across China under both current and future climate scenarios. Moreover, we identified key climate factors that influence their potential distributions. Our findings revealed that S. adnata and S. javanica are predominantly shaped by temperature seasonality and mean diurnal range, respectively, whereas S. williamsii is significantly affected by the precipitation of the wettest month. Currently, S. williamsii is primarily distributed in north and central south China (covering 9.57 × 105 km2), S. javanica is prevalent in the south and east regions (covering 6.41×105 km2), and S. adnata predominantly thrives in the southwest China (covering 1.99×105 km2). Under future climate change scenarios, it is anticipated that S. adnata may migrate to higher latitudes while S. javanica may shift to lower latitudes. However, potentially suitable areas for S. williamsii may contract under certain scenarios for the years 2050 and 2090, with an expansion trend under the SSP585 scenario for the year 2090. Our study emphasizes the importance of climatic variables in influencing the potential geographic distribution of Sambucus species. These findings provide valuable theoretical insights for the preservation, cultivation, and utilization of Sambucus medicinal plant resources in the context of ongoing climate change.

Genetic and histological relationship between pheromone-secreting tissues of the musk gland and skin of juvenile Chinese forest musk deer (Moschus berezovskii Flerov, 1929). / 中国幼年林麝（Moschus berezovskii Flerov, 1929ï¼‰é¦™è ºå’Œçš®è‚¤åˆ†æ³Œä¿¡æ¯ç´ çš„é—ä¼ å’Œç»„ç»‡å­¦å ³ç³».

BACKGROUND: The musk glands of adult male Chinese forest musk deer (Moschus berezovskii Flerov, 1929) (FMD), which are considered as special skin glands, secrete a mixture of sebum, lipids, and proteins into the musk pod. Together, these components form musk, which plays an important role in attracting females during the breeding season. However, the relationship between the musk glands and skin of Chinese FMD remains undiscovered. Here, the musk gland and skin of Chinese FMD were examined using histological analysis and RNA sequencing (RNA-seq), and the expression of key regulatory genes was evaluated to determine whether the musk gland is derived from the skin. METHODS: A comparative analysis of musk gland anatomy between juvenile and adult Chinese FMD was conducted. Then, based on the anatomical structure of the musk gland, skin tissues from the abdomen and back as well as musk gland tissues were obtained from three juvenile FMD. These tissues were used for RNA-seq, hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), western blot (WB), and quantitative real-time polymerase chain reaction (qRT-PCR) experiments. RESULTS: Anatomical analysis showed that only adult male FMD had a complete glandular organ and musk pod, while juvenile FMD did not have any well-developed musk pods. Transcriptomic data revealed that 88.24% of genes were co-expressed in the skin and musk gland tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis found that the genes co-expressed in the abdomen skin, back skin, and musk gland were enriched in biological development, endocrine system, lipid metabolism, and other pathways. Gene Ontology (GO) enrichment analysis indicated that the genes expressed in these tissues were enriched in biological processes such as multicellular development and cell division. Moreover, the Metascape predictive analysis tool demonstrated that genes expressed in musk glands were skin tissue-specific. qRT-PCR and WB revealed that sex-determining region Y-box protein 9 (Sox9),Caveolin-1 (Cav-1), andandrogen receptor (AR) were expressed in all three tissues, although the expression levels differed among the tissues. According to the IHC results, Sox9 and AR were expressed in the nuclei of sebaceous gland, hair follicle, and musk gland cells, whereas Cav-1 was expressed in the cell membrane. CONCLUSIONS: The musk gland of Chinese FMD may be a derivative of skin tissue, and Sox9, Cav-1, and AR may play significant roles in musk gland development.

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.

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.

Brain-derived estrogen: a critical player in maintaining cognitive health of aged female rats, possibly involving GPR30.

Brain-derived estrogen is an endogenous neuroprotective agent, whether and how might this protective function with aging, especially postmenopausal drops in circulating estrogen, remain unclear. We herein subjected 6, 14, and 18 Mon female rats to mimic natural aging, and found that estrogen synthesis is more active in the healthy aged brain, as evidenced by the highest levels of mRNA and protein expression of aromatase, the key enzyme of E2 biosynthesis, among the three groups. Aromatase knockout in forebrain neurons (FBN-Aro-/-) impaired hippocampal and cortical neurons, and cognitive function in 18 Mon rats, compared to wild-type controls. Furthermore, estrogen nuclear receptors (ERα/ß) displayed opposite changes, with a significant ERα decrease and ERß increase, while membrane receptor GPR30 expressed stably in hippocampus during aging. Intriguingly, GPR30, but not ERα and ERß, was decreased by FBN-Aro-/-. The results indicate that GPR30 is more sensitive to brain local E2 synthesis. Our findings provide evidence of a critical role for brain-derived estrogen in maintaining healthy brain function in older individuals, possibly involving GPR30.

Metformin improves fish sperm quality by regulating glucose uptake capacity during in vitro storage.

A suitable additive for fish sperm storage in vitro is necessary for artificial reproduction. In this study, we evaluated the effects of different concentrations (100, 200, 400, and 800 µmol/L) of metformin (Met) on Schizothorax prenanti and Onychostoma macrolepis sperm under storage in vitro for 72 h. Compared with the control group, 400 µmol/L Met was more effective at improving the quality and fertilization capacity of S. prenanti sperm by increasing the adenosine triphosphate (ATP) content within the sperm. Further study found that Met stabilized the ATP level by enhancing the glucose uptake in S. prenanti sperm, and this effect might be associated with the activation of AMP-activated protein kinase (AMPK) in sperm. In this study, we also found that glucose could be absorbed by the sperm of S. prenanti, which was mainly accumulated in the midpiece of S. prenanti sperm, where mitochondria were located. In addition, Compound C significantly inhibited the beneficial effects of Met on the quality and glucose uptake capacity of S. prenanti sperm by inhibiting AMPK phosphorylation. These results revealed that AMPK played an important role in vitro sperm storage, and Met maintained ATP content and increased the storage time of S. prenanti sperm in vitro for 72 h, possibly due to Met enhanced glucose uptake capacity of sperm by activating AMPK. Similarly, the beneficial effects of Met on S. prenanti sperm were also found in O. macrolepis sperm, suggesting that Met may hold great promise for the practice of storing fish in vitro.

Generally, what matters most to fish sperm is a good storage condition in vitro that can both ensure its high motility after fresh water activation and avoid the damage of the nonactivated state. An appropriate additive can provide suitable storage conditions for sperm. Therefore, a suitable additive of fish sperm is necessary for fish to promote effective artificial reproduction. In this study, we evaluated the effects of different concentrations of metformin (Met) on fish sperm under storage in vitro. Compared with the control group, Met was more effective at improving the quality and fertilization capacity of fish by increasing the adenosine triphosphate (ATP) content within the sperm. Further study found that Met stabilized the ATP level by enhancing the glucose uptake in fish sperm, and this effect might be associated with the activation of AMP-activated protein kinase (AMPK) in sperm. The beneficial effects of Met on fish sperm suggest that Met may hold great promise for the practice of storing fish in future vitro storage.