H2AK119ub1 differentially fine-tunes gene expression by modulating canonical PRC1- and H1-dependent chromatin compaction.

Polycomb repressive complex 1 (PRC1) is a key transcriptional regulator in development via modulating chromatin structure and catalyzing histone H2A ubiquitination at Lys119 (H2AK119ub1). H2AK119ub1 is one of the most abundant histone modifications in mammalian cells. However, the function of H2AK119ub1 in polycomb-mediated gene silencing remains debated. In this study, we reveal that H2AK119ub1 has two distinct roles in gene expression, through differentially modulating chromatin compaction mediated by canonical PRC1 and the linker histone H1. Interestingly, we find that H2AK119ub1 plays a positive role in transcription through interfering with the binding of canonical PRC1 to nucleosomes and therefore counteracting chromatin condensation. Conversely, we demonstrate that H2AK119ub1 facilitates H1-dependent chromatin condensation and enhances the silencing of developmental genes in mouse embryonic stem cells, suggesting that H1 may be one of several possible pathways for H2AK119ub1 in repressing transcription. These results provide insights and molecular mechanisms by which H2AK119ub1 differentially fine-tunes developmental gene expression.

SRSF2 plays an unexpected role as reader of m5C on mRNA, linking epitranscriptomics to cancer.

A common mRNA modification is 5-methylcytosine (m5C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of m5C and impaired SRSF2 m5C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m5C recognition and the impact of the prevalent leukemia-associated mutation SRSF2P95H. We show that SRSF2 binding and m5C colocalize within transcripts. Furthermore, knocking down the m5C writer NSUN2 decreases mRNA m5C, reduces SRSF2 binding, and alters RNA splicing. We also show that the SRSF2P95H mutation impairs the ability of the protein to read m5C-marked mRNA, notably reducing its binding to key leukemia-related transcripts in leukemic cells. In leukemia patients, low NSUN2 expression leads to mRNA m5C hypomethylation and, combined with SRSF2P95H, predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver.

A CYP78As-small grain4-coat protein complex â ¡ pathway promotes grain size in rice.

CYP78A, a cytochrome P450 subfamily that includes rice (Oryza sativa L.) BIG GRAIN2 (BG2, CYP78A13) and Arabidopsis thaliana KLUH (KLU, CYP78A5), generate an unknown mobile growth signal (referred to as a CYP78A-derived signal) that increases grain (seed) size. However, the mechanism by which the CYP78A pathway increases grain size remains elusive. Here, we characterized a rice small grain mutant, small grain4 (smg4), with smaller grains than its wild type due to restricted cell expansion and cell proliferation in spikelet hulls. SMG4 encodes a multidrug and toxic compound extrusion (MATE) transporter. Loss of function of SMG4 causes smaller grains while overexpressing SMG4 results in larger grains. SMG4 is mainly localized to endoplasmic reticulum (ER) exit sites (ERESs) and partially localized to the ER and Golgi. Biochemically, SMG4 interacts with coat protein complex Ⅱ (COPⅡ) components (Sar1, Sec23, and Sec24) and CYP78As (BG2, GRAIN LENGTH 3.2 [GL3.2], and BG2-LIKE 1 [BG2L1]). Genetically, SMG4 acts, at least in part, in a common pathway with Sar1 and CYP78As to regulate grain size. In summary, our findings reveal a CYP78As-SMG4-COPⅡ regulatory pathway for grain size in rice, thus providing new insights into the molecular and genetic regulatory mechanism of grain size.

Spotlight on histone H2A variants: From B to X to Z.

Chromatin, the functional organization of DNA with histone proteins in eukaryotic nuclei, is the tightly-regulated template for several biological processes, such as transcription, replication, DNA damage repair, chromosome stability and sister chromatid segregation. In order to achieve a reversible control of local chromatin structure and DNA accessibility, various interconnected mechanisms have evolved. One of such processes includes the deposition of functionally-diverse variants of histone proteins into nucleosomes, the building blocks of chromatin. Among core histones, the family of H2A histone variants exhibits the largest number of members and highest sequence-divergence. In this short review, we report and discuss recent discoveries concerning the biological functions of the animal histone variants H2A.B, H2A.X and H2A.Z and how dysregulation or mutation of the latter impacts the development of disease.

Sirt6 protects cardiomyocytes against doxorubicin-induced cardiotoxicity by inhibiting P53/Fas-dependent cell death and augmenting endogenous antioxidant defense mechanisms.

Sirt6, a class III NAD+-dependent deacetylase of the sirtuin family, is a highly specific H3 deacetylase and plays important roles in regulating cellular growth and death. The induction of oxidative stress and death is the critical mechanism involved in cardiomyocyte injury and cardiac dysfunction in doxorubicin-induced cardiotoxicity, but the regulatory role of Sirt6 in the fate of DOX-impaired cardiomyocytes is poorly understood. In the present study, we exposed Sirt6 heterozygous (Sirt6+/-) mice and their littermates as well as cultured neonatal rat cardiomyocytes to DOX, then investigated the role of Sirt6 in mitigating oxidative stress and cardiac injury in the DOX-treated myocardium. Sirt6 partial knockout or silencing worsened cardiac damage, remodeling, and oxidative stress injury in mice or cultured cardiomyocytes with DOX challenge. Cardiomyocytes infected with adenoviral constructs encoding Sirt6 showed reversal of this DOX-induced damage. Intriguingly, Sirt6 reduced oxidative stress injury by upregulating endogenous antioxidant levels, interacted with oxidative stress-stirred p53, and acted as a co-repressor of p53 in nuclei. Sirt6 was recruited by p53 to the promoter regions of the target genes Fas and FasL and further suppressed p53 transcription activity by reducing histone acetylation. Sirt6 inhibited Fas/FasL signaling and attenuated both Fas-FADD-caspase-8 apoptotic and Fas-RIP3 necrotic pathways. These results indicate that Sirt6 protects the heart against DOX-induced cardiotoxicity by upregulating endogenous antioxidants, as well as suppressing oxidative stress and cell death signaling pathways dependent on ROS-stirred p53 transcriptional activation, thus reducing Fas-FasL-mediated apoptosis and necrosis. •Sirt6 is significantly decreased in DOX-insulted mouse hearts and cardiomyocytes. •Sirt6 attenuates DOX-induced cardiac atrophy, dysfunction and oxidative stress. • Sirt6 reduces oxidative stress injury by upregulating endogenous antioxidants. • Sirt6 interacts with p53 as a co-repressor to suppress p53 transcriptional regulation and inhibits Fas-FasL-mediated apoptosis and necrosis downstream of p53.

HIF-1-dependent heme synthesis promotes gemcitabine resistance in human non-small cell lung cancers via enhanced ABCB6 expression.

Gemcitabine is commonly used to treat various cancer types, including human non-small cell lung cancer (NSCLC). However, even cases that initially respond rapidly commonly develop acquired resistance, limiting our ability to effectively treat advanced NSCLC. To gain insight for developing a strategy to overcome gemcitabine resistance, the present study investigated the mechanism of gemcitabine resistance in NSCLC according to the involvement of ATP-binding cassette subfamily B member 6 (ABCB6) and heme biosynthesis. First, an analysis of ABCB6 expression in human NSCLCs was found to be associated with poor prognosis and gemcitabine resistance in a hypoxia-inducible factor (HIF)-1-dependent manner. Further experiments showed that activation of HIF-1α/ABCB6 signaling led to intracellular heme metabolic reprogramming and a corresponding increase in heme biosynthesis to enhance the activation and accumulation of catalase. Increased catalase levels diminished the effective levels of reactive oxygen species, thereby promoting gemcitabine-based resistance. In a mouse NSCLC model, inhibition of HIF-1α or ABCB6, in combination with gemcitabine, strongly restrained tumor proliferation, increased tumor cell apoptosis, and prolonged animal survival. These results suggest that, in combination with gemcitabine-based chemotherapy, targeting HIF-1α/ABCB6 signaling could result in enhanced tumor chemosensitivity and, thus, may improve outcomes in NSCLC patients.

Terminally exhausted CD8+ T cells contribute to age-dependent severity of respiratory virus infection.

BACKGROUND: Lower respiratory infections are a leading cause of severe morbidity and mortality among older adults. Despite ubiquitous exposure to common respiratory pathogens throughout life and near universal seropositivity, antibodies fail to effectively protect the elderly. Therefore, we hypothesized that severe respiratory illness in the elderly is due to deficient CD8+ T cell responses. RESULTS: Here, we establish an aged mouse model of human metapneumovirus infection (HMPV) wherein aged C57BL/6 mice exhibit worsened weight loss, clinical disease, lung pathology and delayed viral clearance compared to young adult mice. Aged mice generate fewer lung-infiltrating HMPV epitope-specific CD8+ T cells. Those that do expand demonstrate higher expression of PD-1 and other inhibitory receptors and are functionally impaired. Transplant of aged T cells into young mice and vice versa, as well as adoptive transfer of young versus aged CD8+ T cells into Rag1-/- recipients, recapitulates the HMPV aged phenotype, suggesting a cell-intrinsic age-associated defect. HMPV-specific aged CD8+ T cells exhibit a terminally exhausted TCF1/7- TOX+ EOMES+ phenotype. We confirmed similar terminal exhaustion of aged CD8+ T cells during influenza viral infection. CONCLUSIONS: This study identifies terminal CD8+ T cell exhaustion as a mechanism of severe disease from respiratory viral infections in the elderly.

Biomechanical behaviour of a novel bone cement screw in the minimally invasive treatment of Kummell's disease: a finite element study.

OBJECTIVE: To investigate and evaluate the biomechanical behaviour of a novel bone cement screw in the minimally invasive treatment of Kummell's disease (KD) by finite element (FE) analysis. METHODS: A validated finite element model of healthy adult thoracolumbar vertebrae T12-L2 was given the osteoporotic material properties and the part of the middle bone tissue of the L1 vertebral body was removed to make it wedge-shaped. Based on these, FE model of KD was established. The FE model of KD was repaired and treated with three options: pure percutaneous vertebroplasty (Model A), novel unilateral cement screw placement (Model B), novel bilateral cement screw placement (Model C). Range of motion (ROM), maximum Von-Mises stress of T12 inferior endplate and bone cement, relative displacement of bone cement, and stress distribution of bone cement screws of three postoperative models and intact model in flexion and extension, as well as lateral bending and rotation were analyzed and compared. RESULTS: The relative displacements of bone cement of Model B and C were similar in all actions studied, and both were smaller than that of Model A. The minimum value of relative displacement of bone cement is 0.0733 mm in the right axial rotation of Model B. The maximum Von-Mises stress in T12 lower endplate and bone cement was in Model C. The maximum Von-Mises stress of bone cement screws in Model C was less than that in Model B, and it was the most substantial in right axial rotation, which is 34%. There was no substantial difference in ROM of the three models. CONCLUSION: The novel bone cement screw can effectively reduce the relative displacement of bone cement by improving the stability of local cement. Among them, novel unilateral cement screw placement can obtain better fixation effect, and the impact on the biomechanical environment of vertebral body is less than that of novel bilateral cement screw placement, which provides a reference for minimally invasive treatment of KD in clinical practice.

Activity of the new OSBP inhibitor Y18501 against Pseudoperonospora cubensis and its application for the control of cucumber downy mildew.

Y18501 is a new oxysterol-binding protein inhibitor (OSBPI) with a similar structure to oxathiapiprolin. Y18501 showed strong inhibitory activities against Phytophthora spp. and Pseudoperonospora cubensis, with EC50 ranging from 0.0005 to 0.0046 µg/mL. It also had good control efficacy on cucumber downy mildew (CDM) in the green house and in the field, and could effectively inhibit different development stages of P. cubensis, especially for sporangiophore production, sporangial production, mycelium extension, and elongation of germ tube. In addition, Y18501 showed excellent protective and curative activities against P. cubensis. It also had acropetal systemic mobility in the cucumber leaves, and could be taken up and translocated to the upper leaves more effectively from the lower leaves than from the roots. Y18501 had poorer permeability in cucumber leaves compared to oxathiapiprolin. The simultaneous application of Y18501 and chlorothalonil could significantly promote the inhibition of P. cubensis.

DVDR-SRGAN: Differential Value Dense Residual Super-Resolution Generative Adversarial Network.

In the field of single-image super-resolution reconstruction, GAN can obtain the image texture more in line with the human eye. However, during the reconstruction process, it is easy to generate artifacts, false textures, and large deviations in details between the reconstructed image and the Ground Truth. In order to further improve the visual quality, we study the feature correlation between adjacent layers and propose a differential value dense residual network to solve this problem. We first use the deconvolution layer to enlarge the features, then extract the features through the convolution layer, and finally make a difference between the features before being magnified and the features after being extracted so that the difference can better reflect the areas that need attention. In the process of extracting the differential value, using the dense residual connection method for each layer can make the magnified features more complete, so the differential value obtained is more accurate. Next, the joint loss function is introduced to fuse high-frequency information and low-frequency information, which improves the visual effect of the reconstructed image to a certain extent. The experimental results on Set5, Set14, BSD100, and Urban datasets show that our proposed DVDR-SRGAN model is improved in terms of PSNR, SSIM, and LPIPS compared with the Bicubic, SRGAN, ESRGAN, Beby-GAN, and SPSR models.

Young Leaf White Stripe encodes a P-type PPR protein required for chloroplast development.

Pentatricopeptide repeat (PPR) proteins function in post-transcriptional regulation of organellar gene expression. Although several PPR proteins are known to function in chloroplast development in rice (Oryza sativa), the detailed molecular functions of many PPR proteins remain unclear. Here, we characterized a rice young leaf white stripe (ylws) mutant, which has defective chloroplast development during early seedling growth. Map-based cloning revealed that YLWS encodes a novel P-type chloroplast-targeted PPR protein with 11 PPR motifs. Further expression analyses showed that many nuclear- and plastid-encoded genes in the ylws mutant were significantly changed at the RNA and protein levels. The ylws mutant was impaired in chloroplast ribosome biogenesis and chloroplast development under low-temperature conditions. The ylws mutation causes defects in the splicing of atpF, ndhA, rpl2, and rps12, and editing of ndhA, ndhB, and rps14 transcripts. YLWS directly binds to specific sites in the atpF, ndhA, and rpl2 pre-mRNAs. Our results suggest that YLWS participates in chloroplast RNA group II intron splicing and plays an important role in chloroplast development during early leaf development.

Dietary soybean lecithin promoted growth performance and feeding in juvenile Chinese perch (Siniperca chuatsi) could be by optimizing glucolipid metabolism.

To explore the potential benefits of dietary phospholipids (PLs) in fish glucose metabolism and to promote feed culture of Chinese perch (Siniperca chuatsi), we set up six diets to feed Chinese perch (initial mean body weight 37.01 ± 0.20 g) for 86 days, including: Control diet (CT), 1% (SL1), 2% (SL2), 3% (SL3), 4% (SL4) soybean lecithin (SL) and 2% (KO2) krill oil (KO) supplemental diets (in triplicate, 20 fish each). Our study found that the SL2 significantly improved the weight gain rate and special growth rate, but the KO2 did not. In addition, the SL2 diet significantly improved feed intake, which is consistent with the mRNA levels of appetite-related genes (npy, agrp, leptin A). Additionally, in the CT and SL-added groups, leptin A expression levels were nearly synchronized with serum glucose levels. Besides, the SL2 significantly upregulated expression levels of glut2, gk, cs, fas and downregulated g6pase in the liver, suggesting that it may enhance glucose uptake, aerobic oxidation, and conversion to fatty acids. The SL2 also maintained the hepatic crude lipid content unchanged compared to the CT, possibly by significantly down-regulating the mRNA level of hepatic lipase gene (hl), and by elevating serum low-density lipoprotein (LDL) level and intraperitoneal fat ratio in significance. Moreover, the serum high-density lipoprotein levels were significantly increased by PL supplementation, and the SL2 further significantly increased serum total cholesterol and LDL levels, suggesting that dietary PLs promote lipid absorption and transport. Furthermore, dietary SL at 1% level could enhance non-specific immune capacity, with serum total protein level being markedly higher than that in the CT group. In conclusion, it is speculated that the promotion of glucose utilization and appetite by 2% dietary SL could be linked. We suggest a 1.91% supplementation of SL in the diet for the best growth performance in juvenile Chinese perch.

CRISPR screens uncover protective effect of PSTK as a regulator of chemotherapy-induced ferroptosis in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the most common forms of cancer and is associated with poor patient outcomes. The emergence of therapeutic resistance has hampered the efficacy of targeted treatments employed to treat HCC patients to date. In this study, we conducted a series of CRISPR/Cas9 screens to identify genes associated with synthetic lethality capable of improving HCC patient clinical responses. METHODS: CRISPR-based loss-of-function genetic screens were used to target 18,053 protein-coding genes in HCC cells to identify chemotherapy-related synthetic lethal genes in these cells. Synergistic effects were analyzed through in vitro and in vivo analyses, while related mechanisms were explored through RNA-seq and metabolomics analyses. Potential inhibitors of identified genetic targets were selected through high-throughput virtual screening. RESULTS: The inhibition of phosphoseryl-tRNA kinase (PSTK) was found to increase HCC cell sensitivity to chemotherapeutic treatment. PSTK was associated with the suppression of chemotherapy-induced ferroptosis in HCC cells, and the depletion of PSTK resulted in the inactivation of glutathione peroxidative 4 (GPX4) and the disruption of glutathione (GSH) metabolism owing to the inhibition of selenocysteine and cysteine synthesis, thus enhancing the induction of ferroptosis upon targeted chemotherapeutic treatment. Punicalin, an agent used to treat hepatitis B virus (HBV), was identified as a possible PSTK inhibitor that exhibited synergistic efficacy when applied together with Sorafenib to treat HCC in vitro and in vivo. CONCLUSIONS: These results highlight a key role for PSTK as a mediator of resistance to targeted therapeutic treatment in HCC cells that functions by suppressing ferroptotic induction. PSTK inhibitors may thus represent ideal candidates for overcoming drug resistance in HCC.

"Phoenix in Flight": an unique fruit morphology ensures wind dispersal of seeds of the phoenix tree (Firmiana simplex (L.) W. Wight).

BACKGROUND: Many seed plants produce winged diaspores that use wind to disperse their seeds. The morphology of these diaspores is directly related to the seed dispersal potential. The majority of winged diaspores have flat wings and only seeds; however, some angiosperms, such as Firmiana produce winged fruit with a different morphology, whose seed dispersal mechanisms are not yet fully understood. In this study, we observed the fruit development of F. simplex and determined the morphological characteristics of mature fruit and their effects on the flight performance of the fruit. RESULTS: We found that the pericarp of F. simplex dehisced early and continued to unfold and expand during fruit development until ripening, finally formed a spoon-shaped wing with multiple alternate seeds on each edge. The wing caused mature fruit to spin stably during descent to provide a low terminal velocity, which was correlated with the wing loading and the distribution of seeds on the pericarp. When the curvature distribution of the pericarp surface substantially changed, the aerodynamic characteristics of fruit during descent altered, resulting in the inability of the fruit to spin. CONCLUSIONS: Our results suggest that the curved shape and alternate seed distribution are necessary for the winged diaspore of F. simplex to stabilize spinning during wind dispersal. These unique morphological characteristics are related to the early cracking of fruits during development, which may be an adaptation for the wind dispersal of seeds.

Cell-to-cell transmission of HIV-1 from provirus-activated cells to resting naïve and memory human primary CD4 T cells is highly efficient and requires CD4 and F-actin but not chemokine receptors.

Latently infected cells harboring replication-competent proviruses represent a major barrier to HIV-1 cure. One major effort to purge these cells has focused on developing the "shock and kill" approach for forcing provirus reactivation to induce cell killing by viral cytopathic effects, host immune responses, or both. We conducted kinetic and mechanistic studies of HIV-1 protein expression, virion production, and cell-to-cell virus transmission during provirus reactivation. Provirus-activated ACH-2 cells stimulated with romidepsin (RMD) or PMA produced Nef early, and then Env and Gag in parallel with the appearance of virions. Env on the surface of provirus-activated cells and cellular F-actin were critical in the formation of virological synapses to mediate cell-to-cell transmission of HIV-1 from provirus-activated cells to uninfected cells. This HIV-1 cell-to-cell transmission was substantially more efficient than transmission seen via cell-free virus spread and required F-actin remodeling and CD4, but not chemokine receptors. Resting human primary CD4+ T cells including naïve and memory subpopulations and, especially the memory CD4+ T cells, were highly susceptible to HIV-1 infection via cell-to-cell transmission. Cell-to-cell transmission of HIV-1 from provirus-activated cells was profoundly decreased by protease inhibitors (PIs) and neutralizing antibodies (nAbs) that recognize the CD4-binding site (CD4bs) such as VRC01, but not by reverse transcriptase (RT) inhibitor Emtricitabine (FTC). Therefore, our results suggest that PIs with potent blocking abilities should be used in clinical application of the "shock and kill" approach, most likely in combination with CD4bs nAbs, to prevent new HIV-1 infections.

Mogrol suppresses lung cancer cell growth by activating AMPK-dependent autophagic death and inducing p53-dependent cell cycle arrest and apoptosis.

Lung carcinoma is the leading cause of cancer-related death worldwide. Chemotherapy remains the cornerstone of lung cancer treatment. Unfortunately, most types of cancer will develop resistance to chemotherapies over the time. One of the efforts to prevent the chemotherapy resistance is to find alternative chemotherapy drugs. Mogrol has been found to have antitumor activity. However, little is known about the pharmacological mechanisms underlying the suppression of mogrol on lung cancers. In this study, we observed that mogrol exposure significantly reduced the tumor volume and weight in tumor-bearing nude mice without obvious effect on body weight and cardiac function. Mogrol also significantly inhibited the proliferation and migration of lung cancer cells, including non-small-cell lung carcinoma cells, A549, H1299, H1975 and SK-MES-1 cells, with no obvious effect on control human bronchial epithelial cells (HBE). Further studies revealed that mogrol stirred excessive autophagy and autophagic flux, and finally, autophagic cell death, in lung cancer cells, which could be attenuated by autophagy inhibitors, 3-MA and chloroquine. Furthermore, mogrol significantly activated AMPK to induce autophagy and autophagic cell death, which could be abrogated by Compound C, an AMPK inhibitor. In addition, mogrol induced a significant increase in p53 activity in lung cancer cells, accompanied with cell cycle arrest and apoptosis, which could be weakened by p53 silence. Our results indicated that mogrol effectively suppressed lung cancer cells in vivo and in vitro by inducing the excessive autophagy and autophagic cell death via activating AMPK signaling pathway, as well as cell cycle arrest and apoptosis via activating p53 pathway.

Long-term GnRH agonist pretreatment before frozen embryo transfer improves pregnancy outcomes in women with adenomyosis.

RESEARCH QUESTION: Do frozen embryo transfer (FET) cycles following long-term gonadotrophin-releasing hormone agonist (GnRHa) pretreatment have better pregnancy outcomes than fresh embryo transfer cycles with long or ultra-long GnRHa protocol in these patients? DESIGN: This study included 537 women with adenomyosis divided into three groups: (Group A) FET cycles following long-term GnRHa pretreatment (192 patients); (Group B) fresh embryo transfer cycles with the ultra-long GnRHa protocol (241 patients); (Group C) fresh embryo transfer cycles with the long GnRHa protocol (104 patients). RESULTS: The total gonadotrophin dose and stimulation duration were significantly lower in Group A than in Groups B and C. The implantation and live birth rates were significantly higher in Group A than in Groups B and C. In the long-term GnRHa pretreatment and FET treatment of Group A, implantation (odds ratio [OR] 1.729, 95% confidence interval [CI] 1.073-2.788, P = 0.025), clinical pregnancy (OR 1.665, 95% CI 1.032-2.686, P = 0.037) and live birth rates (OR 1.694, 95% CI 1.045-2.746, P = 0.033) increased and miscarriage rate (OR 0.203, 95% CI 0.078-0.530, P = 0.001) decreased when compared with Group C. Comparison of Groups A and B showed that with the long-term GnRHa pretreatment, FET was a protective factor for live birth rate (OR 1.350, 95% CI 1.017-1.792, P = 0.038). CONCLUSION: FET following long-term GnRHa pretreatment has a better IVF/intracytoplasmic sperm injection outcome, and a potential benefit in terms of a lower gonadotrophin dose, and a shorter stimulation duration than fresh embryo transfer combined with a long or ultra-long GnRHa protocol.

Bubbles help male flowers overcome obstacles during pollination in Hydrilla verticillata.

PREMISE: Pollination in many aquatic plants takes place on the water surface, and the male flowers or stamens often produce gas bubbles underwater; however, the generation mechanism and function of these bubbles are unknown. METHODS: A common submerged plant, Hydrilla verticillata, was used as experimental material to observe the structure of male flowers, analyze the process of bubble generation, and simulate the movement process of the male flower with attached gas bubble in water. RESULTS: The aerenchyma inside the male plants of H. verticillata transported the gas produced by the plant's branches during photosynthesis to the male flower, and the formed gas bubbles became attached to the edge of the perianth. The gas accumulation rate in the attached bubbles increased with light intensity. Once the bubble diameter increased to approximately 3.3 mm, the male flowers with the bubble detached from the plant and floated to the water surface. The removal of the attached bubbles did not affect the male flower detached from the plant; however, the surfacing of male flowers without gas bubbles was easily prevented by the plant's branches in the water, and they could not reach the water surface to complete pollen dispersal. CONCLUSIONS: The gas bubbles produced by male flowers of H. verticillata came from the gas produced by branches under light. These bubbles can help ascending male flowers bypass the obstacles in water and reach the surface to complete pollination.

Dietary bile acids reduce liver lipid deposition via activating farnesoid X receptor, and improve gut health by regulating gut microbiota in Chinese perch (Siniperca chuatsi).

The aim of this study is to explore the effects of dietary bile acids (BAs) supplementation on lipid metabolism and gut health of Chinese perch (Siniperca chuatsi), and its possible mechanisms. Two isonitrogenous and isolipidic diets were formulated to supplement different levels of BAs (0 and 900 mg BAs kg-1 diet, respectively). All fish (Initial mean body weight: 171.29 ± 0.77g) were randomly divided into 2 groups (triplicate, 54 fish/group) and were fed with different experimental diets for 56 days, respectively. Dietary exogenous BAs supplementation at the concentration of 900 mg kg-1 significantly increased weight gain and survival rate, and decreased feed conversion ratio. BAs could inhibit lipid synthesis and promote lipid oxidation to reduce lipid deposition by activating farnesoid X receptor (FXR). Dietary BAs supplementation increased the abundance of Lactobacilli in Firmicutes, and the increase of Lactobacillus caused the increase of lactic acid level and the decrease of pH, which might be the reason for the gut villus length and gut wall high in this study. Dietary BAs supplementation increased the levels of catalase and superoxide dismutase and decreased the level of malondialdehyde in the gut and plasma, which might be contributed to the regulating the antioxidant stress phenotype of gut microbiota by the increased abundance of Firmicutes. Then it caused the increase of the globulin level in the plasma, meaning the enhancement of immune state. The increased immunity might also be thought to be responsible for increased survival rate. These results suggest dietary BAs reduce liver lipid deposition via activating FXR, and improve gut health by regulating gut microbiota in Chinese perch.

Development and validation of a model for individualized prediction of cervical insufficiency risks in patients undergoing IVF/ICSI treatment.

BACKGROUND: Women who conceived with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) are more likely to experience adverse pregnancy outcomes than women who conceived naturally. Cervical insufficiency (CI) is one of the important causes of miscarriage and premature birth, however there is no published data available focusing on the potential risk factors predicting CI occurrence in women who received IVF/ICSI treatment. This study aimed to identify the risk factors that could be integrated into a predictive model for CI, which could provide further personalized and clinically specific information related to the incidence of CI after IVF/ICSI treatment. PATIENTS AND METHODS: This retrospective study included 4710 patients who conceived after IVF/ICSI treatment from Jan 2011 to Dec 2018 at a public university hospital. The patients were randomly divided into development (n = 3108) and validation (n = 1602) samples for the building and testing of the nomogram, respectively. Multivariate logistic regression was developed on the basis of pre-pregnancy clinical covariates assessed for their association with CI occurrence. RESULTS: A total of 109 patients (2.31%) experienced CI among all the enrolled patients. Body mass index (BMI), basal serum testosterone (T), gravidity and uterine length were associated with CI occurrence. The statistical nomogram was built based on BMI, serum T, gravidity and uterine length, with an area under the curve (AUC) of 0.84 (95% confidence interval: 0.76-0.90) for the developing cohort. The AUC for the validation cohort was 0.71 (95% confidence interval: 0.69-0.83), showing a satisfactory goodness-of-fit and discrimination ability in this nomogram. CONCLUSION: The user-friendly nomogram which graphically represents the risk factors and a pre-pregnancy predicted tool for the incidence of CI in patients undergoing IVF/ICSI treatment, provides a useful guide for medical staff on individualized decisions making, where preventive measures could be carried out during the IVF/ICSI procedure and subsequent pregnancy.