Search

Background: Over-activated osteoclast (OC) is a major cause of diseases related to bone loss and bone metabolism. Both bone resorption inhibition and apoptosis induction of osteoclast are crucial in treating these diseases. X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) is an important interferon-stimulated and apoptotic gene. However, how XAF1 regulates bone formation and remodeling is unknown. Methods: We generate global and chimeric Xaf1 knockout mouse models and utilize these models to explore the function and mechanism of XAF1 in regulating bone formation and remodeling in vivo and in vitro. Results: We show that XAF1 depletion enhances osteoclast generation in vitro. XAF1 knockout increases osteoclast number and bone resorption, thereby exacerbating bone loss in both OVX and osteolysis models. Activation of XAF1 with BV6 (a potent XIAP inhibitor) suppresses osteoclast formation. Mechanistically, XAF1 deletion decreases osteoclast apoptosis by facilitating the interaction between XIAP and caspase-3/7. Conclusions: Our data illustrates an essential role of XAF1 in controlling osteoclastogenesis in both osteoporosis and osteolysis mouse models and highlights its underlying mechanism, indicating a potential role in clinical treatment.The translational potential of this article: The translation potential of this article is that we first indicated that osteoclast apoptosis induced by XAF1 contribute to the progression of osteoporosis and osteolysis, which provides a novel strategy in the prevention of osteoporosis and osteolysis.

Purpose: To evaluate synthetic magnetic resonance imaging (SyMRI) and iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL-IQ) imaging for a comprehensive evaluation of rotator cuff injuries (RCI). Methods: Ninety-seven patients with RCI were classified into four groups based on the arthroscopic results: (grade II), partial tear (grade III), complete tear (grade IV), and controls (grade I). T1 (Transverse Relaxation Time 1), T2 (Transverse Relaxation Time 2), proton density (PD), and fat fraction (FF) were evaluated using SyMRI and IDEAL-IQ. Measurement reliability was assessed using intraclass correlation coefficients (ICC). The diagnostic potential for grading RCI was evaluated using ordinal regression and ROC analyses. Results: A high measurement reliability (ICC > 0.7) was observed across subregions. T1 and T2 significantly varied across grades, particularly T2 in the lateral subregion between grades III and IV (P < 0.001) and the central subregion between grades II and III (P < 0.001). ROC analyses yielded valuable diagnostic accuracy, including T2 in the lateral subregion with an AUC of 0.891, distinguishing grade I from grade IV. Positive correlations were found between T2 values in specific shoulder subregions and injury grade (r = 0.615 for lateral, r = 0.542 for medial, both P < 0.001). In grade IV, FF was notably increased in the supraspinatus, infraspinatus, and subscapularis muscles compared with grades I-III. There were no significant FF variations in the teres minor muscle among grades. Conclusions: Quantitative MRI parameters from SyMRI and IDEAL-IQ, especially T2 and FF, may classify and assess RCI severity. The results could help improve the accuracy of diagnosing different grades of RCI, offering clinicians additional tools for improving patient outcomes through personalized medicine.

Salt marshes are pivotal in the global carbon cycle, serving as significant contributors to the blue carbon sink. Accurately estimating carbon stock in salt marshes relies on precise vegetation classification. Here, we developed the Salt Marsh Vegetation Classification Network (SVCN), a deep learning algorithm designed to classify three primary vegetation canopies (S. alterniflora, P. australis, and S. mariqueter) spanning from 2016 to 2023 over the Yangtze River estuary, China. The SVCN was initially trained using 412 vegetation samples and Sentinel-1 Synthetic Aperture Radar (SAR) data in 2018. Additionally, we trained three traditional machine learning models – Classification and Regression Trees, Random Forests, and K-Nearest Neighbors – to facilitate a comparative analysis of model performance. Leveraging the classified vegetation outcomes, we conducted salt marsh carbon stock estimations using the InVEST model. The results showed that the SVCN model outperformed the other three models, achieving an overall accuracy of 0.97. Salt marsh carbon stocks in the Yangtze River estuary exhibited an overall increasing trend from 2016 to 2023, with an average annual increase of 3.13 ×103Mg⋅year−1. However, there was a notable decrease of 10.36% in 2017, primarily attributed to reductions in the area covered by S. alterniflora and P. australis, which decreased by 11.18% and 10.11%, respectively. These findings highlight the potential of deep learning models and the incorporation of salt marshes in carbon stock estimates to enhance accuracy.

Summary: Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SCGABA). SCGABA forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTADA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.

Co-firing NH3 with conventional hydrocarbon fuels is an important approach for reducing CO2 emissions in existing combustion systems. Besides CO2, the blending of NH3 would also notably affect soot formation and its oxidation behaviors. In the present study, we focus on the effects of NH3 on the nanostructure and oxidation characteristics of soot produced in diffusion flames of n-heptane/toluene mixtures. Two configurations of laminar co-flow diffusion flame, including both normal and inverse diffusion flames (NDF and IDFs), were used for investigation. High-resolution transmission electron microscopy (HRTEM), Raman spectroscopy (Raman), and Thermogravimetric analysis (TGA) were employed for soot characterization. The HRTEM and Raman spectra showed that with the increase of NH3 blending ratio, the fringe length (La) and the degree of graphitization decreased while the microcrystal tortuosity (Tf) increased. The results are in consistent with TGA analysis which suggests the promoting effects of NH3 on the soot oxidation reactivity. Difference between NDF and IDF with respect to the soot nanostructure and oxidation activity were discussed. It is our hope that the present results could deepen our understanding on the effects of NH3 on soot nanostructure and oxidation behavior and benefit the design of particulate filters for combustion devices fueled with hydrocarbon/NH3 mixtures.

Synthetic single-stranded oligonucleotides play crucial roles in DNA amplification reactions for various applications, such as serving as primers, enabling magnetic separation, and generating dsDNA for subsequent digestion. Typically, these oligos are added in excess to ensure rapid binding to their intended targets. However, while performing rolling circle amplification (RCA) using phi29 DNA polymerase, we observed a decrease in amplification efficiency when oligos were present in the reaction. This phenomenon was consistently observed in two separate laboratories, prompting this study to delve into the root causes responsible for the decline in RCA efficiency. The lowered efficiency was consistent regardless of the manufacturer or any mutations in the phi29 polymerase. We identified several variables that influenced RCA efficiency, mainly the length of the oligos used and the presence of modifications, particularly those obstructing 3’ end digestion. This strongly suggests that the exonuclease domain of phi29 DNA polymerase is responsible for the competition-based inhibition. Our investigation shows that even picomole quantities of oligos can significantly reduce total DNA production during the phi29 DNA polymerase-mediated amplification process. Conversely, the addition of oligos to the reaction did not impede the efficiency of Bst 3.0 polymerase, likely due to the lack of an exonuclease domain of said polymerase. While increasing the quantity of phi29 DNA polymerase in the reaction partially alleviated the adverse effects of excess oligos, we believe it is crucial to carefully optimize the oligo quantities to achieve maximum amplification of the desired targets.

Microphytobenthos (MPB) are central to benthic tidal flat ecological networks. Large-scale information on total MPB biomass is difficult to obtain from traditional in-situ measurements. Here, we assessed the effectiveness of using surface sediment properties as proxies for predicting the total (depth-integrated) MPB biomass with Sentinel satellite data. First, the best subset regression was applied to the in-situ data to determine the properties that best predict the biomass decay rate with depth (sampling every cm up to 10 cm depth). Then, data from a controlled laboratory experiment were used to analyse the spectral response to different sediment properties (i.e., variations in sediment grain size, organic matter and water content). Subsequently, an algorithm was developed to obtain the spatial distribution of the sediment properties and the depth-integrated total MPB biomass from remote sensing data. Finally, we presented a case study in which the seasonal dynamics of total (depth-integrated) MPB biomass were obtained from Sentinel-2 Multispectral Instrument (MSI) satellite data using the Google Earth Engine (GEE) platform. The results showed that (1) the vertical distribution of MPB biomass on a tidal flat could be predicted by the surface MPB biomass, median grain-size (D50) and water content (W0) of the sediment (top 1 cm); (2) the near infrared (NIR) band absorption depth was a key feature in estimating D50 and W0; and (3) the seasonal variation in the total (depth-integrated) MPB biomass was prominent in Chongming Dongtan, Changjiang Estuary. We concluded that the depth-integrated exponential decay algorithm was useful for estimating total MPB biomass and, combined with mappable sediment-surface data, could help map the total MPB biomass in estuarine tidal flats at a large scale.

Wetlands are globally critical for human survival and Earth's sustainable development. However, wetlands are experiencing rapid degradation and loss due to pollution, reclamation, climate change, invasions, etc. Ramsar sites are globally recognized as wetland hotspots that have been designated Wetlands of International Importance under the Ramsar Convention. However, the long-term trends of change that affect these sites remain unclear. This study explored the ecological changes and characteristics of Ramsar sites using 7 ecological indicators from three aspects: vegetation status, hydrological dynamics and anthropogenic disturbance, with the support of 36-year dense Landsat imagery and the trend and mutation analysis algorithms of Theil-Sen and BreakoutDetection. The results showed that (1) for the long-term trend, the ecological status of 55% of China's Ramsar sites experienced a trend of degradation, and the remaining Ramsar sites showed a trend of restoration in the past 36 years. (2) After the mutation was analysed, 47% of the Ramsar sites showed an environmental and ecological improvement trend in the recent period. (3) More than 50% of Ramsar sites were found to have ecological reversals in vegetation status and hydrological dynamics in the past 36 years.

Photovoltaic (PV) solar energy generation attracts considerable attention to archive carbon neutrality goals worldwide. Geospatial data describing the PV system based on satellite images are critical for PV deployment. However, it remains challenging to obtain relative data in coastal zones due to frequent cloud cover. There have also been relatively few studies on spatial analysis of PV development in terms of solar resources and the energy demands. Therefore, this study took Chinese coastal provinces as example, and proposed a random forest classification method with information on morphology, optics, and SAR to address cloud pollution. The results obtained were analyzed with geographical and socioeconomic factors to determine its development status. The results have shown that (1) by October 2022, the total PV area in Chinese coastal provinces reached 837.3 km2, with an overall accuracy of 96.9 % and a Kappa coefficient of 0.91. Water-based PV represents 33.7 % which tended to be distributed near the shoreline. (2) Bounded by the Huai River, the PV density in the north was 9.0 km2 per 104 km2, which is more than twice that in the south. The development of water-based PV is a key reason for the high PV construction density in coastal areas. (3) PV distribution was slightly mismatched with solar resource and power demand, especially in Liaoning and Guangdong. Liaoning has relatively high potential for PV development. The study findings can play a key role in evaluation of PV power generation, development potential, and ecological environmental impacts.

Purpose: To select individuals and families with a low genetic burden for age-related macular degeneration (AMD), to inform the clinical diagnosis of macular disorders, and to find novel genetic variants associated with maculopathies. Design: Genetic association study based on targeted and whole-exome sequencing. Participants: A total of 758 subjects (481 individuals with maculopathy and 277 controls), including 316 individuals in 72 families. Methods: We focused on 150 genes involved in the complement, coagulation, and inflammatory pathways. Single-variant tests were performed on 7755 variants shared among ≥ 5 subjects using logistic regression. Gene-based tests were used to evaluate aggregate effects from rare and low-frequency variants (at minor allele frequency [MAF] ≤ 5% or ≤ 1%) in a gene using burden tests. For families whose affected members had a low burden of genetic risk based on known common and rare variants related to AMD, we searched for rare variants (MAF < 0.001) whose risk alleles occurred in ≥ 80% of affected individuals but not in controls. Immunohistochemistry was performed to determine the protein expression of a novel gene (coagulation factor II thrombin receptor-like 2 [F2RL2]) in retinal tissues. Main Outcome Measures: Genotypes and phenotypes of macular degeneration. Results: We confirmed the association of a synonymous variant in complement factor H (Ala473, rs2274700, proxy to intronic rs1410996, r2 = 1) with maculopathy (odds ratio, 0.64; P = 4.5 × 10–4). Higher AMD polygenic risk scores (PRSs) were associated with intermediate and advanced AMD. Among families with low PRSs and no known rare variants for maculopathy, we identified 2 novel, highly penetrant missense rare variants in ADAM15, A disintegrin and metalloprotease, metallopeptidase domain 15 (p.Arg288Cys) and F2RL2 (p.Leu289Pro). Immunohistochemistry analyses revealed F2RL2 protein expression in cone photoreceptor outer segments and Müller glia cells of human and pig retinas. Coagulation factor II thrombin receptor-like 2 expression appeared increased in fibrotic areas in advanced AMD samples with neovascularization, suggesting that F2RL2 may play a role in the progression to advanced macular disease. Conclusions: New missense rare variants in the genes ADAM15 and F2RL2 were associated with maculopathies. Results suggest that novel genes related to the coagulation and immune pathways may be involved in the pathogenesis of macular diseases.

Corneal neovascularization (CoNV) leads to visual impairment, affecting over 1.4 million people in the United States per year. It is caused by a variety of pathologies, such as inflammation, hypoxia, and limbal barrier dysfunction. Injection of the anti-vascular endothelial growth factor (VEGF) drug KH902 (conbercept) can inhibit CoNV but requires repeated dosing that produces associated side effects, such as cornea scar. To explore more efficacious and long-lasting treatment of CoNV, we employed recombinant adeno-associated virus (rAAV)2 and rAAV8 vectors to mediate KH902 expression via a single intrastromal injection and investigated its anti-angiogenic effects and safety in both alkali-burn- and suture-induced CoNV mouse models. Our results showed that rAAV-mediated KH902 mRNA expression in the cornea was sustained for at least 3 months after a single intrastromal injection. Moreover, the expression level of rAAV8-KH902 far exceeded that of rAAV2-KH902. A single-dose rAAV8-KH902 treatment at 8 × 108 genome copies (GCs) per cornea dramatically inhibited CoNV for an extended period of time in mouse CoNV models without adverse events, whereas the inhibition of CoNV by a single intrastromal administration of the conbercept drug lasted for only 10−14 days. Overall, our study demonstrated that the treatment of CoNV with a single dose of rAAV8-KH902 via intrastromal administration was safe, effective, and long lasting, representing a novel therapeutic strategy for CoNV.

Although coastal aquaculture ponds provide high-quality fish protein for billions of people, they are threatened by urbanization, pollution, and climate change. Moreover, colossal aquaculture ponds pose damages such as natural wetland shrinkage and water quality deterioration. However, understanding the trends and drivers of coastal aquaculture ponds on a national scale remains a challenge. In this study, a decision-tree classifier was used to quantify the spatiotemporal distribution of aquaculture ponds over last 30 years in 12 provinces located on the coast of China. Moreover, we analyzed their trends and drivers, including geographical conditions, socioeconomic factors, and development policies. The key results of the study include the following: (1) from 1990 to 2020, the cumulative area and holding area of aquaculture ponds reached 21997.90 km2 and 9613.66 km2, representing 3.7-fold and 1.6-fold increase, respectively, than the 1990 values. Based on geographical conditions, most aquaculture ponds tend to be located in coastal plains and bays following the distribution of low-lying land. (2) Influenced by different levels of socioeconomic development and changed policies, the holding area of aquaculture ponds experienced a “rapidly increasing period” from 1990 to 2011, growing by 246 km2 per year; “stable period” between 2011 and 2017; and “sharply shrinking period” after 2017 declining by 417 km2/year. (3) Coastal land reclamation played a critical role in the expansion of aquaculture ponds by cumulatively contributing approximately 22% of the land resource in the past 30 years. In the future, as a result of increasing land competition, the extent of aquaculture ponds on the China coast tends to decrease continually.

Enhancement interaction between polybutadiene (PB) nanoparticle and polypropylene (PP) matrix by grafts via hydrogen bonding was verified and characterized by dynamic rheological analysis. The introduction of acrylamide (AM) facilitated PB uniform distribution in PP and strengthened interfacial interaction. The correlated structure based on H-bonding interaction leading to the viscoelastic nonlinearity, which restricted polymer relaxation and exhibited different rheological responses. The formation of correlated structure is an energetically favorable process driven by enthalpy, while the dynamics of construction is controlled by diffusion of the binding groups correspondingly, thus, the reconstruction and recoverability depend on the thermodynamic equilibrium distorted by either the shearing or the temperature. Therefore, the recovery ratio increases from 77.31%, 96.53%, to 98.87%, for the blend with identical composition, when increment of temperature from 180, 200–220 °C, is attributed to relaxation enhancement for both the decrement of local viscosity and the acceleration of diffusion.

Long noncoding RNAs (lncRNAs) are a group of RNAs that lack protein-coding ability, with lengths greater than 200 nucleotides. Increasing evidence has indicated that they mediate multiple physiological and pathological processes by regulating gene expression at the epigenetic, transcriptional, post-transcriptional, and translational levels. The deregulation of lncRNAs was demonstrated to have tumor suppressive or oncogenic effects, and thus, these molecules play vital regulatory roles in tumor initiation and progression. Small nucleolar RNA hostgene 7 (SNHG7) is a lncRNA located on chromosome 9q34.3. Different studies have explored the potential role of SNHG7 in the development and progression of multiple human malignancies such as bladder, breast, colorectal, esophageal, gastric, and prostate cancer, as well as osteosarcoma, among others, and high expression predicts poor prognosis and poor survival for such patients. Moreover, this molecule can promote proliferation and metastasis, while inhibiting apoptosis in cancer cells. The present review highlights the latest insights into the expression, functional roles, and molecular mechanisms of SNHG7 in different human malignancies.

IL-33 may play a role in the vascular remodelling of hypoxic pulmonary hypertension (PH) but the precise mechanisms are still unclear. We hypothesized that hypoxia promotes expression of IL-33 and its receptor ST2 on vascular endothelial cells, which in turn leads to dysfunction of vascular endothelial cells and smooth muscle cells contributing to PH. Immunohistochemistry showed that immunoreactivity for IL-33 and ST2 was significantly increased in lung tissue of murine model of hypoxia-induced PH (HPH) and of subjects with bronchiectasis-PH. trans-Thoracic echocardiography showed that haemodynamic changes and right ventricular hypertrophy associated with HPH were significantly abrogated in St2−/− compared with WT mice. Administration of IL-33 further exacerbated these changes in the hypoxia-exposed WT mice. In vitro, hypoxia significantly increased IL-33/ST2 expression by human pulmonary arterial endothelial cells (HPAECs), while exogenous IL-33 enhanced proliferation, adhesiveness and spontaneous angiogenesis of HPAECs. Knockdown of endogenous Il33 or St2 using siRNA transfection significantly suppressed these effects in both normoxic and hypoxic culture-conditions. Deletion of the St2 gene attenuated hypoxia-induced, elevated lung expression of HIF-1α/VEGFA/VEGFR-2/ICAM-1, while administration of exogenous VEGFA partially reversed the attenuation of the haemodynamic indices of PH. Correspondingly, knockdown of the St2 or Hif1α genes almost completely abrogated IL-33-induced expression of HIF-1α/VEGFA/VEGFR-2 by HPAECs in vitro. Further, IL-33-induced angiogenesis by HPAECs was extensively abrogated by knockdown of the Hif1α/Vegfa or Vegfr2 genes. These data suggest that hypoxia induces elevated expression of IL-33/ST2 by HPAECs which, at least partly by increasing downstream expression of HIF-1α and VEGF initiates vascular remodelling resulting in HPH. Keywords: IL-33, Hypoxic pulmonary hypertension, Hypoxia inducible factor 1, Vascular endothelial growth factor

Esophageal cancer (EC) is a serious digestive malignancy and is a leading cause of cancer-related mortality. Apart from genetic mutations, many epigenetic alterations including DNA methylation and histone modifications associated with chromatin remodeling have been identified in the regulation of gene expression in EC. Recently, noncoding RNAs, and mainly lncRNAs and miRNAs, have been revealed to be involved in the epigenetic regulation of EC. In this review, we focus on describing new insights on epigenetic processes associated with noncoding RNAs, which have been characterized to be responsible for the development and progression of EC.

The molecular mechanisms involved in induced pluripotent stem cells (iPSCs) generation are poorly understood. The cell death machinery of apoptosis-inducing caspases have been shown to facilitate the process of iPSCs reprogramming. However, the effect of other cell death processes, such as programmed necrosis (necroptosis), on iPSCs induction has not been studied. In this study, we investigated the role of receptor-interacting protein kinase 3 (RIP3), an essential regulator of necroptosis, in reprogramming mouse embryonic fibroblast cells (MEFs) into iPSCs. RIP3 was found to be upregulated in iPSCs compared to MEFs. Deletion of RIP3 dramatically suppressed the reprogramming of iPSCs (~82%). RNA-seq analysis and qRT-PCR showed that RIP3 KO MEFs expressed lower levels of genes that control cell cycle progression and cell division and higher levels of extracellular matrix-regulating genes. The growth rate of RIP3 KO MEFs was significantly slower than WT MEFs. These findings can partially explain the inhibitory effects of RIP3 deletion on iPSCs generation and show for the first time that the necroptosis kinase RIP3 plays an important role in iPSC reprogramming. In contrast to RIP3, the kinase and scaffolding functions of RIPK1 appeared to have distinct effects on reprogramming. Keywords: Reprogramming, Programmed necrosis, Necroptosis, Cell death, RIPK3, RIPK, RIP

ABSTRACT: Outbreaks of short beak and dwarfism syndrome (SBDS), caused by a novel goose parvovirus (NGPV), have occurred in China since 2015. The NGPV, a single-stranded DNA virus, is thought to be vertically transmitted. However, the mechanism of NGPV immune evasion remains unclear. In this study, we investigated the impact of NGPV infection on the Cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway in duck embryonic fibroblast (DEF) cells. Our findings demonstrate that NGPV infection stimulates the mRNA expression of cGAS but results in weak IFN-β induction. NGPV impedes the expression of IFN-β and downstream interferon-stimulated genes, thereby reducing the secretion of IFN-β induced by interferon-stimulating DNA (ISD) and poly (I: C). RNA-seq results show that NGPV infection downregulates interferon mRNA expression while enhancing the mRNA expression of inflammatory factors. Additionally, the results of viral protein over-expression indicate that VP1 exhibits a remarkable ability to inhibit IFN-β expression compared to other viral proteins. Results indicated that only the intact VP1 protein could inhibit the expression of IFN-β, while the truncated proteins VP1U and VP2 do not possess such characteristics. The immunoprecipitation experiment showed that both VP1 and VP2 could interact with IRF7 protein, while VP1U does not. In summary, our findings indicate that NGPV infection impairs the host's innate immune response by potentially modulating the expression and secretion of interferons and interferon-stimulating factors via IRF7 molecules, which are regulated by the VP1 protein.

ABSTRACT: Photoperiod is an important environmental factor that influences seasonal reproduction behavior in birds. Birds translate photoperiodic information into neuroendocrine signals through deep brain photoreceptors (DBPs). OPN5 has been considered candidate DBPs involved in regulating seasonal reproduction in birds. We found that OPN5 could mediate light to regulate the follicle development in ducks. In this study, we further verified the effect of OPN5 on follicular development in Shan Partridge ducks by immunizing against the extracellular domain (ECD) of OPN5. We investigated the specific regulatory mechanism of photoperiod mediated by OPN5 on the reproductive activity of ducks. The trial randomly divided 120 Shan Partridge ducks into 3 groups with different treatments: the immunization of OPN5 group was done at d0, d15, d30, and d40 with 1 mL of vaccine containing OPN5 protein (thus containing 1, 1, 0.5, and 0.5 mg of OPN5-KLH protein), and the control group (CS and CL groups) was injected at the same time with the same dose of OPN5-uncontained blank vaccine. The group of CS (900 lux), OPN5 (600 lux), and CL (600 lux) lasted for 40 d in 12 L:12 D photoperiods, respectively. Then, the groups of CS, OPN5, and CL subsequently received 12 L:12 D, 12 L:12 D, and 17 L:7 D light treatments for 33 d, respectively. The ducks were caged in 3 constant rooms with the same feeding conditions for each group, free water, and limited feeding (150 g per duck each day). Duck serum and tissue samples were collected at d 40, d 62, and d 73 (n = 12). It was found that before prolonged light, the group of immunization (group OPN5) and the group of strong light intensity (group CS) were higher than the group of CL in egg production. Subsequent to prolonged light, the group CL in egg production rose about the same as the group immunization, while the strong light group (group CS) was lower. Group OPN5 increased the ovarian index of ducks, and both the immunization of group OPN5 and group CL (extended light) increased the thickness of the granular layer and promoted the secretion of E2, P4, LH, and PRL hormones. Compared with group CS, group CL and OPN5 increased the mRNA level and protein expression of OPN5 in the hypothalamus on d 62 and d 73 (P < 0.05). The gene or protein expression patterns of GnRH, TRH, TSHβ, DIO2, THRβ, VIP, and PRL were positively correlated with OPN5, whereas the gene expression patterns of GnIH and DIO3 were negatively correlated with OPN5. The results showed that immunization against OPN5 could activate the corresponding transmembrane receptors to promote the expression of OPN5, up-regulate the expression of TSHβ and DIO2, and then regulate the HPG axis-related genes to facilitate the follicular development of Shan Partridge ducks. In addition, in this experiment, prolonging the photoperiod or enhancing the light intensity could also enhance follicle development, but the effect was not as significant as immunizing against OPN5. Our results will offer beneficial data and more supportive shreds of evidence in favor of elucidating the role of OPN5 in relation to photoperiods and reproduction.

ABSTRACT: The mitochondrial quality control system is crucial in maintaining cellular homeostasis during environmental stress. Granulosa cells are the main cells secreting steroid hormones, and mitochondria are the key organelles for steroid hormone synthesis. The impact of the mitochondrial quality control system on granulosa cells’ steroid hormone synthesis and survival under heat stress is still unclear. Here, we showed that acute heat stress induces mitochondrial damage and significantly increases the number of mitophagy-like vesicles in the cytoplasm of duck ovary granulosa cells at the ultra-structural level. Meanwhile, we also found heat stress significantly increased mitochondrial fission and mitophagy-related protein expression levels both in vivo and in vitro. Furthermore, by confocal fluorescence analysis, we discovered that LC3 was distributed spot-like manner near the nucleus in the heat treatment group, and the LC3 spots and lysosomes were colocalized with Mito-Tracker in the heat treatment group. We further detected the mitophagy-related protein in the cytoplasm and mitochondria, respectively. Results showed that the PINK1 protein was significantly increased both in cytoplasm and mitochondria, while the LC3-Ⅱ/LC3-Ⅰ ratio increase only occurred in mitochondrial. In addition, the autophagy protein induced by acute heat treatment was effectively inhibited by the mitophagy inhibitor CysA. Finally, we demonstrated that the alteration of cellular mitophagy by siRNA interference with Drp1 and PINK1 inhibited the steroid synthesis of granulosa cells and increased cell apoptosis. Study provides strong evidence that the Drp1 regulated PINK1-dependent mitophagy pathway protects follicular granulosa cells from acute heat stress-induced injury.

Adding pomace or juice runoff during maceration is a traditional winemaking process. To mitigate the negative effects of rainfall during harvest and examine the effects of adjusting the pomace ratio during fermentation on the flavor profile of Marselan grape wines, the prefermentation addition of Petit Manseng grape pomace (PAP) and prefermentation juice runoff (PJR) was determined. The phenolic and volatile compounds were investigated using HPLC–MS and GC–MS. PAP enriched the flavanols and PJR enriched the pigment and copigment matrix. Approximate 10% increase in the ratio of pomace promoted the formation of anthocyanin derivatives. The increased pomace ratio reduced the concentration of volatile compounds without impacting the aroma quality. Sensory analysis revealed PAP wines scored higher for acidity and astringency and PJR wines scored higher for color. In conclusion, an appropriate increase in the pomace ratio of approximately 10% can enhance the color and mouthfeel of the wine while having a limited influence on aroma.

Recently, revealing the terroir influence on wine chemical features has drawn increasing interest. This study aimed to explain how wine flavonoid signatures were altered by vineyard parcel, harvest ripeness, vintage and bottle aging. Six commercial Cabernet Sauvignon vineyards were selected in the Manas region to produce wines at three harvest ripeness in three seasons (2019–2021) and aged for three years. The six vineyards had little difference in mesoclimate conditions while varying greatly in soil composition. Results showed high vineyard pH (> 8.5) could accelerate grape ripening rate and increase wine flavonol concentration. Vineyards with moderate nutrition produced wines with abundant anthocyanin derivatives and maintained color characteristics during aging. The role of detailed anthocyanin derivatives in regulating wine color was clarified. As the harvest ripeness elevated, wine’s flavonoid profiles were altered and gained a higher red color intensity. This work provides chemical mechanisms underlying single-vineyard wines and a theoretical basis for targeted wine production.

Summary: In this protocol, we present a modified gradient coating strategy for zinc anodes. We describe steps for synthesizing electrodes, measuring electrochemistry, and assembling and testing batteries. The protocol can be applied for broadening design ideas of functional interface coating.For complete details on the use and execution of this protocol, please refer to Chen et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Objectives: Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS). Method: An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated. Results: The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215−4.916) for moderate selenium-deficient counties and 16.002 (14.706−17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061−1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00–8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14–50.16). Conclusion: Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

The PBL (Perfobond Leiste) shear key has advantages such as high load capacity and high restraint capacity. However, at the same time, there are also problems such as insufficient deformation capacity and low stiffness along the weak axis direction. In addition, shear key performance degradation, ductility, and other problems are not yet clear under the reciprocal seismic action. To this end, a folded perfobond shear key is proposed in this paper to solve the problems of insufficient deformation capacity and uneven stiffness distribution of the traditional PBL shear key. At the same time, numerical analysis is carried out to investigate the seismic performance of the shear key under earthquakes, such as stiffness degradation, ductility, and energy dissipation. Through the push-out test, it is found that the steel plate outside the shear key deforms, showing a certain semi-rigid characteristic; concrete forms a trapezoidal constraint area centered on shear keys, and the constraint effect is significantly improved compared with the point constraint of studs. On the whole, under the condition of a similar shear section, the bearing capacity of the shear key is 1.5 times that of the stud. The ductility coefficient is above 3.0, showing good deformation ability. Through parameter analysis, it is found that the bearing capacity of shear keys increases with the increase of web width-thickness ratio, but the deformation capacity degenerates. The opening rate mainly affects the embedded effect of shear keys and concrete. Based on the fitting analysis, the variation laws of web width influence coefficient γB, web height influence coefficient γH, and embedded effect influence coefficient γD are obtained, and the calculation formula of shear key bearing capacity is proposed. Finally, based on the push-out test, the hysteretic behavior of the shear key is studied. It is found that the load-displacement hysteretic curve of the shear key is full, the ductility coefficient is 4.2, and the equivalent viscous damping coefficient is 0.27, which shows good seismic capacity. In summary, the new shear key realizes the good unity of bearing capacity and deformation and has high engineering application value.

ABSTRACT: This study sought to understand the regulation mechanism of OPN5 through the TSH-DIO2/DIO3 pathway mediated photoperiod on the breeding activity of short-day breeding birds. In this study, the reproductive activity of Magang goose was regulated by artificial light, and the reproductive activity of the ganders were determined according to the daily laying rate of female geese. The testicular development and the serum reproductive hormone concentrations of ganders were measured during the reproductive period (d 0), the reproductive degeneration period (d 13 and 27) and the resting period (d 45). The mRNA and protein expression patterns of OPN5, the HPG axis reproductive genes, and TSH-DIO2/DIO3 pathway related genes were examined. Results showed that the laying rate of geese and the gonadal indices (GSI) decreased gradually after the photoperiod increased. Histological observation found that the spermatogenic function of the testis was normal on d 0 and 13, while degeneration occurred by d 27 and 45. Serum testosterone, FSH, and LH concentration showed a slight increase on d 13, followed by a sharp decrease on d 27 and 45 (P < 0.01), while PRL concentrations were low on d 0 and 13, and increased rapidly on d 27 and 45 (P < 0.01).The expression pattern of GnRH, FSH, LH, and THRβ mRNA were similar, with high levels on d 0 and 13 and a decreasing trend on d 27 and 45 (P < 0.05 or P < 0.01); and GnRHR mRNA levels were higher on d 13 (P < 0.05), but then had decreased by d 27 and 45 (P < 0.01). The expression pattern of GnIH and GnIHR was similar, which was opposite to that of GnRHR. VIP, PRL, and PRLR increased gradually and peaked on d 45 (P < 0.01). The expression trend of TRH, TSHβ, and DIO2 was similar to that of GnRHR, and the expression abundance increased on d 13, and then decreased on d 27 and 45. GnRH protein expression was significantly higher than during the other 3 periods (P < 0.01) while the GnIH protein levels were extremely low on d 0, had gradually increased by d 13, and significantly increased by d 27 and 45 (P < 0.01). The protein expression trends of THR and DIO2 were similar to that of GNIH. DIO3 protein expression was low on d 0 and 13, and increased by d 27 and 45. These results suggest that when the photoperiod increased, the hypothalamus OPN5 gene and protein were upregulated and the pituitary TSHβ, TSHR, and hypothalamus THRβ, TRH, and DIO2 were downregulated, and thus the reproductive activity of geese was inhibited.

Summary: Background: There were no reports on the associations of aortic arch calcification (AAC) measured by chest X-ray with all-cause mortality and cardiovascular disease (CVD) in older general population. Moreover, previous studies of hemodialysis patients showed that AAC was correlated with left ventricular hypertrophy (LVH) and predicted CVD jointly. Whether the effects remained in the general population is unknown. We examined the associations of AAC with all-cause mortality and CVD in general population and the risk associated with the coexistence of AAC and LVH. Methods: Presence and severity (grades 0-2) of AAC were measured by chest X-ray, and LVH was identified by 12-lead electrocardiogram in 27,166 Chinese aged 50+ years free of CVD from Guangzhou Biobank Cohort Study. Multivariate Cox regressions were used to examine associations of AAC and LVH with outcomes. Findings: During an average follow-up of 14·3 years, 5,350 deaths and 4,012 CVD occurred. Compared to those without AAC at baseline, those with AAC had higher risks of all-cause mortality (HR 1·24, 95% CI 1·17-1·31) and CVD (HR 1·22, 95% CI 1·14-1·30), with dose-response relationship (P ≤ 0·001). Furthermore, those with coexistence of AAC and LVH had higher risks of all-cause mortality (HR 1·72, 95% CI 1·37-2·15) and CVD (HR 1·80, 95% CI 1·40-2·32) than those without AAC and LVH. Interpretation: As chest X-ray has been performed commonly for health screening and in hospital patients when first admitted, AAC measured by chest X-ray can be further applied to assist cardiovascular risk stratification in the community and clinical settings. Funding: The Natural Science Foundation of China (No. 81941019).

ABSTRACT: Stocking density critically affects the growth and subsequent performance of animals in modern poultry production. This study investigated the effects of stocking density on ovarian development, ovarian maturation, and the mRNA expression of key genes in the reproductive axis during the rearing period of Shan-ma ducks. The experiments involved 180 healthy 7-wk-old Shan-ma ducks and randomly divided into low stocking density (LSD; n = 30, density = 5 birds/m2), medium stocking density (MSD; n = 60, density = 10 birds/m2) and high stocking density groups (HSD; n = 90, density = 15 birds/m2), for rearing. After examining ovarian development and measuring hormone levels in the plasma and expression levels of key regulatory genes in the reproductive axis at 19 wk of rearing, analysis of the gonad index analysis, reflecting stocking density, uncovered statistically significant differences. The gonad index of the LSD group was significantly higher than those of the MSD and HSD groups (P < 0.01), while no significant difference was observed between the MSD and HSD groups. pre-ovulatory follicles (POFs) and small yellow follicles (SYFs) development was only apparent in the LSD group, with the large white follicles (LWFs) number of this group being significantly higher than that of the MSD group (P < 0.05). The blood levels of E2 (estradiol), P4 (progesterone), and T (testosterone) were significantly higher in the LSD group than in the MSD and HSD groups (P < 0.05 or 0.01). Also, the levels of both P4 and T were significantly higher in the MSD group than in the HSD group (P < 0.01). The gene expression levels of GnRHR, FSH, AMHR, and FSHR were significantly increased in the LSD group compared to the MSD and HSD groups (P < 0.05 or 0.01), while the expression levels of GnIHR and GDF9 were significantly decreased in the LSD and MSD groups compared to the HSD group (P < 0.05 or 0.01). Steroid biosynthesis pathway genes such as StAR, CYP11A1, 3β-HSD, CYP19A1, and BMP15 were significantly downregulated at greater stocking densities (P < 0.05 or 0.01). Likewise, the protein expression of StAR, 3β-HSD, and CYP19A1 was also significantly decreased (P < 0.05 or 0.01). These results demonstrate that both medium and high stocking densities suppressed the expression of the key reproduction-promoting factors, while the expression level of the key reproductive inhibitory factors was enhanced. Therefore, rates of ovarian development and maturation could be reduced by a high stocking density leading to a delay in reproduction performance during the rearing period of Shan-ma ducks.

Summary: In traditional dual-ion systems, the cathode usually is employed as anion-storage materials. Herein, we propose a new dual-ion hybrid supercapacitor with reverse anion/cation-storage mechanism, consisting of a mesoporous (MPs) VN anode as a pivotal anion-storage material and K2-xMn8O16 nanosheet arrays grown on carbon cloth (NSs/CC) as (K-storage) cathode. During charge/discharge, the anode and cathode reversibly store/release OH− ions and K+ ions, respectively. Herein, the MPs VN as anion-storage electrode can operate in an alkaline condition and deliver a high capacitance of 251 mF cm−2 with desired low-voltage plateau. More importantly, benefiting from unique reverse dual-ion mechanism, the (MPs VN-K2-xMn8O16 NSs/CC) hybrid device displays excellent rate performance and satisfying area capacitance along with good durability of 92.2% after 10,000 cycles at a scan rate of 100 mV s−1. It offers new ideas to expand the range of anion-storage materials in dual-ion hybrid supercapacitors.

ABSTRACT: Resveratrol, a natural antioxidant, anti-inflammatory plant extract, was found to have a protective effect in poultry subjected to heat stress. In this study, we strove to characterize resveratrol on intestinal of duck exposed to acute heat stress and investigate the underlying mechanism. A total of 120 Shan-ma ducks (60 days old) were randomly divided into 2 groups. The control group was fed a basal diet, and the resveratrol group was fed a basal diet supplemented with 400 mg/kg resveratrol. Animals in 2 groups were kept at a temperature of 24°C ± 2°C for 15 d. Then, animals of both groups were placed in an artificial climate room at 39°C. Twelve ducks of each group were sacrificed for sampling at 0, 30, and 60 min, respectively. Results indicated that resveratrol increased the ratio of villus height to crypt depth, increased the number of goblet cells, and reduced the histopathological damage of jejunum caused by acute heat stress. Furthermore, the gene expression of heat shock proteins (HSP60, HSP70, and HSP90) and tight junction proteins (CLDN1 and OCLN) was significantly increased in the resveratrol group compared to that in the control groups. Simultaneously, resveratrol significantly activated the SIRT1-NRF1/NRF2 signaling pathways, improved ATP level of jejunum, and increased SOD and CAT antioxidant enzymes activities. In addition, we found that the NF-κB/NLRP3 inflammasome signaling pathways were repressed under acute heat stress. Meanwhile, supplement resveratrol further inhibited the NLRP3 inflammasome pathway, decreased protein level of NLRP3 and caspase1 p20, reduced the secretion of IL-1β. Taken together, our results indicate that resveratrol against the oxidative damage and inflammation injury in duck jejunum induced by heat stress via active SIRT1 signaling pathways.

Discus fish have a variety of body colors including pigmentary and structural colors, studies on specific substances and related metabolic pathways associated with body coloration, however, are scarce to the present. Here, we used single-color (blue, yellow and white) of discus for comparative metabolomics analysis of pigmentary and structural coloration. Statistical model showed significant separations between three colors of discus, suggesting the distinct metabolite profiles of discus pigmentary and structural colors. More astaxanthin was found in yellow discus, which might be the cause of yellow pigmentary color. Moreover, docosahexaenoic acid, arachidonic acid, linoleic acid, eicosapentaenoic acid, 1-stearoyl-2-oleoyl-sn-glycerol 3-phosphocholine, dodecanoic acid and myristic acid related to lipid metabolism and pathways of ABC transporters and biosynthesis of unsaturated fatty acids were more enriched in yellow discus. More adenine, xanthine and hypoxanthine were enriched in blue discus, which might account for the blue structural color. Moreover, amino acids associated with purine biosynthesis, e.g., L-alanine and L-isoleucine, were reduced but pathways of protein digestion and absorption, aminoacyl-tRNA biosynthesis, purine metabolism and glycine, serine and threonine metabolism were enriched in blue discus. Overall, these results reveal specific chromophores and related metabolic pathways involved in pigmentary and structural coloration of discus fish. SIGNIFICANCE: We detected specific chromophores present in skin of pigmentary and structural colors of discus and revealed potential metabolic pathways associated with body coloration. These results contribute to our understanding of the mechanism of body color formation in discus fish., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recent studies have implied that activation of AMP-dependent protein kinase (AMPK) could protect myocardial cells from oxygen glucose deprivation-re-oxygenation (OGD/R). The aim of the present study is to test whether GSK621, a novel and direct AMPK activator, could exert myocardial cell protection against OGD/R. We show that in AC16 human myocardial cells and primary murine myocardiocytes GSK621 dose-dependently activated AMPK signaling. GSK621 pretreatment potently inhibited OGD/R-induced viability reduction, cell death and apoptosis in AC16 cells and primary myocardiocytes. Furthermore, GSK621 attenuated OGD/R-induced reactive oxygen species production and oxidative injury in the myocardial cells. AMPKα1 knockdown (via targeted shRNA), knockout (via a CRISPR/Cas9 construct) or dominant negative mutation (T172A) not only blocked GSK621-induced AMPK activation, but also nullified GSK621-mediated myocardial cell protection against OGD/R. Further studies demonstrated that GSK621 activated AMPK downstream Nrf2 signaling. Contrarily, Nrf2 silencing by targeted shRNAs almost abolished GSK621-induced anti-OGD/R myocardial cell protection. We conclude that GSK621 protects myocardial cells from OGD/R through activation of AMPK-dependent signaling., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This paper reports a nanomagnetic polyhedral oligomeric silsesquioxanes (POSS)-directing strategy toward construction of molecularly imprinted hybrid materials for antibiotic residues determination in milk samples. The imprinted polymeric layer was facilely obtained through the copolymerization of active vinyl groups present on the nanomagnetic POSS (Fe3O4@POSS) surface and functional monomer (methacrylic acid) binding with template (enrofloxacin). Herein, the octavinyl POSS acted as not only the building blocks for hybrid rigid architectures but also the cross-linker for the formation of effective recognition sites during the imprinting process. The molecularly imprinted Fe3O4@POSS nanoparticles (Fe3O4@MI-POSS) demonstrated much higher adsorption capacity and selectivity toward enrofloxacin molecules and its analogs than the non-imprinted Fe3O4@POSS (Fe3O4@NI-POSS) materials. The imprinted particles were applied as a selective sorbent in solid-phase extraction focusing upon sample pretreatment in complex matrices prior to chromatographic analysis. The three FQs (ofloxacin, enrofloxacin, danofloxacin) could be selectively extracted from the biological matrix, while the matrix interferences were effectively eliminated simultaneously under the optimum extraction conditions. A simple, rapid and sensitive method based on the Fe3O4@MI-POSS material combined with HPLC-UV detection was then established for the simultaneous determination of three FQs from milk samples. The average recoveries of the three FQs were in the range of 75.6-108.9%. The relative standard deviations of intra- and inter-day ranging from 2.91 to 8.87% and from 3.6 to 11.5%, respectively. The limits of detections (S/N=3) were between 1.76 and 12.42 ng mL(-1). It demonstrates the effectiveness of trace analysis in complicated biological matrices utilizing magnetic separation in combination with molecularly imprinted solid-phase extraction, the rich chemistry of POSS makes it possible to be an ideal platform for generating molecular imprinted hybrid materials is also exhibited., (Copyright © 2014 Elsevier B.V. All rights reserved.)