Transposable element accumulation drives size differences among polymorphic Y Chromosomes in Drosophila.

Y Chromosomes of many species are gene poor and show low levels of nucleotide variation, yet they often display high amounts of structural diversity. Dobzhansky cataloged several morphologically distinct Y Chromosomes in Drosophila pseudoobscura that differ in size and shape, but the molecular causes of their large size differences are unclear. Here we use cytogenetics and long-read sequencing to study the sequence content of polymorphic Y Chromosomes in D. pseudoobscura We show that Y Chromosomes differ almost twofold in size, ranging from 30 to 60 Mb. Most of this size difference is caused by a handful of active transposable elements (TEs) that have recently expanded on the largest Y Chromosome, with different elements being responsible for Y expansion on differently sized D. pseudoobscura Y's. We show that Y Chromosomes differ in their heterochromatin enrichment and expression of Y-enriched TEs, and also influence expression of dozens of autosomal and X-linked genes. The same helitron element that showed the most drastic amplification on the largest Y in D. pseudoobscura independently amplified on a polymorphic large Y Chromosome in Drosophila affinis, suggesting that some TEs are inherently more prone to become deregulated on Y Chromosomes.

The maize transcription factor CCT regulates drought tolerance by interacting with Fra a 1, E3 ligase WIPF2, and auxin response factor Aux/IAA8.

Plants are commonly exposed to abiotic stressors, which can affect their growth, productivity, and quality. Previously, the maize transcription factor ZmCCT was shown to be involved in the photoperiod response, delayed flowering, and quantitative resistance to Gibberella stalk rot. In this study, we demonstrate that ZmCCT can regulate plant responses to drought. ZmCCT physically interacted with ZmFra a 1, ZmWIPF2, and ZmAux/IAA8, which localized to the cell membrane, cytoplasm, and nucleus, respectively, both in vitro and in vivo in a yeast two-hybrid screen in response to abiotic stress. Notably, ZmCCT recruits ZmWIPF2 to the nucleus, which has strong E3 self-ubiquitination activity dependent on its RING-H2 finger domain in vitro. When treated with higher indole-3-acetic acid/abscisic acid ratios, the height and root length of Y331-ΔTE maize plants increased. Y331-ΔTE plants exhibited increased responses to exogenously applied auxin or ABA compared to Y331 plants, indicating that ZmCCT may be a negative regulator of ABA signalling in maize. In vivo, ZmCCT promoted indole-3-acetic acid biosynthesis in ZmCCT-overexpressing Arabidopsis. RNA-sequencing and DNA affinity purification-sequencing analyses showed that ZmCCT can regulate the expression of ZmRD17, ZmAFP3, ZmPP2C, and ZmARR16 under drought. Our findings provide a detailed overview of the molecular mechanism controlling ZmCCT functions and highlight that ZmCCT has multiple roles in promoting abiotic stress tolerance.

An injectable and thermosensitive hydrogel with nano-aided NIR-II phototherapeutic and chemical effects for periodontal antibacteria and bone regeneration.

Periodontitis is a common public health problem worldwide and an inflammatory disease with irregular defect of alveolar bone caused by periodontal pathogens. Both antibacterial therapy and bone regeneration are of great importance in the treatment of periodontitis. In this study, injectable and thermosensitive hydrogels with 3D networks were used as carriers for controlled release of osteo-inductive agent (BMP-2) and Near Infrared Region-II (NIR-II) phototherapy agents (T8IC nano-particles). T8IC nano-particles were prepared by reprecipitation and acted as photosensitizer under 808 nm laser irradiation. Besides, we promoted photodynamic therapy (PDT) through adding H2O2 to facilitate the antibacterial effect instead of increasing the temperature of photothermal therapy (PTT). Hydrogel + T8IC + Laser + BMP-2 + H2O2 incorporated with mild PTT (45 °C), enhanced PDT and sustained release of BMP-2. It was present with excellent bactericidal effect, osteogenic induction and biosafety both in vitro and in vivo. Besides, immunohistochemistry staining and micro-CT analyses had confirmed that PTT and PDT could promote bone regeneration through alleviating inflammation state. Altogether, this novel approach with synergistic antibacterial effect, anti-inflammation and bone regeneration has a great potential for the treatment of periodontitis in the future.

Quantifying the impacts of posture changes on office worker productivity: an exploratory study using effective computer interactions as a real-time indicator.

BACKGROUND: Working in a standing posture is considered to improve musculoskeletal comfort and can help enhance office workers' performance in the long term. However, there is a lack of a quantitative, real-time measure that reflects on whether office workers can immediately become more concentrated and work more efficiently when they switch to a standing posture. METHODS: To tackle this problem, this study proposed that the number of effective computer interactions could be used as a real-time indicator to measure the productivity of office workers whose work is primarily computer-based. Using this metric, we conducted an exploratory study to investigate the correlation between posture and productivity changes at a 10-minute resolution for eight participants. RESULTS: The study found that when allowed to use sit-stand desks to adjust postures, participants chose to switch to standing posture for about 47 min on average once a day; standing work was most frequent between 2:30 - 4:00 pm, followed by 10:30 - 11:30 am, during which time the number of computer interactions also became higher, showing a significant positive correlation. In addition, participants were approximately 6.5% more productive than when they could only work in a sitting posture. CONCLUSION: This study revealed that posture changes could have an immediate improvement in productivity.

Epidemiology of influenza under the coronavirus disease 2019 pandemic in Nanjing, China.

PURPOSE: Since the pandemic of coronavirus disease-19 (COVID-19), the incidence of influenza has decreased significantly, but there are still few reports in the short period before and after the pandemic period. This study aimed to explore influenza activity and dynamic changes before and during the pandemic. METHODS: A total of 1 324 357 influenza-like illness (ILI) cases were reported under the ILI surveillance network from January 1, 2018, to September 5, 2021, in Nanjing, of which 16 158 cases were detected in a laboratory. Differences in ILI and influenza were conducted with the χ2 test. RESULTS: The number of ILI cases accounted for 8.97% of outpatient and emergency department visits. The influenza-positive ratio (IPR) was 7.84% in ILI cases. During the COVID-19 pandemic, ILI% and IPR dropped by 6.03% and 11.83% on average, respectively. Besides this, IPR rose slightly in Week 30-35 of 2021. Not only differences in gender, age, and employment status, but also the circulating strains had changed from type A to B through the COVID-19 pandemic. CONCLUSION: The level of influenza activity was severely affected by COVID-19, but it seems that it is inevitable to be vigilant against the co-circulation in the future.

The effect of nutritional status on clinical outcome in lung transplantation.

BACKGROUND AND OBJECTIVES: Nutritional status greatly impacts the clinical outcome of the patients receiving lung transplantation. The objective of this study was to evaluate the effect of nutritional status on the clinical outcome in lung transplant recipients. METHODS AND STUDY DESIGN: A single-center retrospective study was conducted including 73 patients received lung transplantation from December 2015 to April 2022 in the Affiliated Henan Provincial People's Hospital of Zhengzhou University. Data were collected from the hospital information system. The records of BMI, malnutrition defined by the Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria, hemoglobin and plasma albumin before operation were accessed. The primary outcome assessed was survival or mortality represented by Kaplan-Meier survival curves; the log-rank test and multivariate Cox proportional hazards regression were used to evaluate the influence of each factor on survival. RESULTS: Kaplan-Meier survival analysis showed that malnutrition, hemoglobin and plasma albumin were predictors of survival in lung transplantation (Log Rank p<0.05). Multivariate Cox regression showed that pre-operative hemoglobin <130 g/L (HR 2.532, p=0.036) and plasma albumin <35 g/L (HR 2.723, p=0.016) were associated with the decreased survival rate. CONCLUSIONS: Preoperative anemia and hypoalbuminemia increase the mortality risk of the lung transplantation patients. Pre-operative nutrition support, therefore, is likely to be critical for improving clinical outcome in patients undergoing lung transplantation.

Optimization of ultrasound-assisted aqueous two phase extraction of polyphenols from olive leaves.

In this study, polyphenols from olive leaves was extracted by ultrasound-assisted aqueous two phase extraction (UAATPE). Based on single factor experiment and response surface methodology (RSM), the optimum extraction conditions of polyphenols contained 29% (w/w) (NH4)2SO4, 35% (w/w) ethanol, pH 6.7, and 45 °C. The maximum extraction yield of polyphenols and oleuropein content were 34.06 mg/g and 44.13 mg/L, respectively. Compared with ultrasound-assisted extraction (UAE) and aqueous two phase extraction (ATPE), the extraction yield of polyphenols by UAATPE was 9.48 and 61.19% higher, respectively. In addition, the extract of UAATPE had higher purity. The results of antioxidant activity showed that polyphenols extracted by UAATPE had stronger DPPH and hydroxyl radicals scavenging ability and reducing power. Therefore, UAATPE is an efficient method for extracting polyphenols from olive leaves.

A transposon-directed epigenetic change in ZmCCT underlies quantitative resistance to Gibberella stalk rot in maize.

A major resistance quantitative trait locus, qRfg1, significantly enhances maize resistance to Gibberella stalk rot, a devastating disease caused by Fusarium graminearum. However, the underlying molecular mechanism remains unknown. We adopted a map-based cloning approach to identify the resistance gene at qRfg1 and examined the dynamic epigenetic changes during qRfg1-mediated maize resistance to the disease. A CCT domain-containing gene, ZmCCT, is the causal gene at the qRfg1 locus and a polymorphic CACTA-like transposable element (TE1) c. 2.4 kb upstream of ZmCCT is the genetic determinant of allelic variation. The non-TE1 ZmCCT allele is in a poised state, with predictive bivalent chromatin enriched for both repressive (H3K27me3/H3K9me3) and active (H3K4me3) histone marks. Upon pathogen challenge, this non-TE1 ZmCCT allele was promptly induced by a rapid yet transient reduction in H3K27me3/H3K9me3 and a progressive decrease in H3K4me3, leading to disease resistance. However, TE1 insertion in ZmCCT caused selective depletion of H3K4me3 and enrichment of methylated GC to suppress the pathogen-induced ZmCCT expression, resulting in disease susceptibility. Moreover, ZmCCT-mediated resistance to Gibberella stalk rot is not affected by photoperiod sensitivity. This chromatin-based regulatory mechanism enables ZmCCT to be more precise and timely in defense against F. graminearum infection.

A positive feedback loop involving Gcm1 and Fzd5 directs chorionic branching morphogenesis in the placenta.

Chorioallantoic branching morphogenesis is a key milestone during placental development, creating the large surface area for nutrient and gas exchange, and is therefore critical for the success of term pregnancy. Several Wnt pathway molecules have been shown to regulate placental development. However, it remains largely unknown how Wnt-Frizzled (Fzd) signaling spatiotemporally interacts with other essential regulators, ensuring chorionic branching morphogenesis and angiogenesis during placental development. Employing global and trophoblast-specific Fzd5-null and Gcm1-deficient mouse models, combining trophoblast stem cell lines and tetraploid aggregation assay, we demonstrate here that an amplifying signaling loop between Gcm1 and Fzd5 is essential for normal initiation of branching in the chorionic plate. While Gcm1 upregulates Fzd5 specifically at sites where branching initiates in the basal chorion, this elevated Fzd5 expression via nuclear ß-catenin signaling in turn maintains expression of Gcm1. Moreover, we show that Fzd5-mediated signaling induces the disassociation of cell junctions for branching initiation via downregulating ZO-1, claudin 4, and claudin 7 expressions in trophoblast cells at the base of the chorion. In addition, Fzd5-mediated signaling is also important for upregulation of Vegf expression in chorion trophoblast cells. Finally, we demonstrate that Fzd5-Gcm1 signaling cascade is operative during human trophoblast differentiation. These data indicate that Gcm1 and Fzd5 function in an evolutionary conserved positive feedback loop that regulates trophoblast differentiation and sites of chorionic branching morphogenesis.

Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1.

Recognition of methylated histone tail lysine residues by tudor domains plays important roles in epigenetic control of gene expression and DNA damage response. Previous studies revealed the binding of methyllysine in a cage of aromatic residues, but the molecular mechanism by which the sequence specificity for surrounding histone tail residues is achieved remains poorly understood. In the crystal structure of a trimethylated histone H3 lysine 4 (H3K4) peptide bound to the tudor-like domains of Spindlin1 presented here, an atypical mode of methyllysine recognition by an aromatic pocket of Spindlin1 is observed. Furthermore, the histone sequence is recognized in a distinct manner involving the amino terminus and a pair of arginine residues of histone H3, and disruption of the binding impaired stimulation of pre-RNA expression by Spindlin1. Our analysis demonstrates considerable diversities of methyllysine recognition and sequence-specific binding of histone tails by tudor domains, and the revelation furthers the understanding of tudor domain proteins in deciphering epigenetic marks on histone tails.

Resistance, mechanism, and fitness cost of specific bacteriophages for Pseudomonas aeruginosa.

The bacteriophage is an effective adjunct to existing antibiotic therapy; however, in the course of bacteriophage therapy, host bacteria will develop resistance to bacteriophages, thus affecting the efficacy. Therefore, it is important to describe how bacteria evade bacteriophage attack and the consequences of the biological changes that accompany the development of bacteriophage resistance before the bacteriophage is applied. The specific bacteriophage vB3530 of Pseudomonas aeruginosa (P. aeruginosa) has stable biological characteristics, short incubation period, strong in vitro cleavage ability, and absence of virulence or resistance genes. Ten bacteriophage-resistant strains (TL3780-R) were induced using the secondary infection approach, and the plaque assay showed that vB3530 was less sensitive to TL3780-R. Identification of bacteriophage adsorption receptors showed that the bacterial surface polysaccharide was probably the adsorption receptor of vB3530. In contrast to the TL3780 parental strain, TL3780-R is characterized by the absence of long lipopolysaccharide chains, which may be caused by base insertion of wzy or deletion of galU. It is also intriguing to observe that, in comparison to the parent strain, the bacteriophage-resistant strains TL3780-R mostly exhibited a large cost of fitness (growth rate, biofilm formation, motility, and ability to produce enhanced pyocyanin). In addition, TL3780-R9 showed increased susceptibility to aminoglycosides and chlorhexidine, which may be connected to the loss and down-regulation of mexX expression. Consequently, these findings fully depicted the resistance mechanism of P. aeruginosa to vB3530 and the fitness cost of bacteriophage resistance, laying a foundation for further application of bacteriophage therapy.IMPORTANCEThe bacteriophage is an effective adjunct to existing antibiotic therapy; However, bacteria also develop defensive mechanisms against bacteriophage attack. Thus, there is an urgent need to deeply understand the resistance mechanism of bacteria to bacteriophages and the fitness cost of bacteriophage resistance so as to lay the foundation for subsequent application of the phage. In this study, a specific bacteriophage vB3530 of P. aeruginosa had stable biological characteristics, short incubation period, strong in vitro cleavage ability, and absence of virulence or resistance genes. In addition, we found that P. aeruginosa may lead to phage resistance due to the deletion of galU and the base insertion of wzy, involved in the synthesis of lipopolysaccharides. Simultaneously, we showed the association with the biological state of the bacteria after bacteria acquire bacteriophage resistance, which is extremely relevant to guide the future application of therapeutic bacteriophages.

Wnt6 is essential for stromal cell proliferation during decidualization in mice.

Postimplantation uterine development involves extensive stromal cell proliferation and decidual transformation with polyploidization, which is essential for normal pregnancy establishment. However, it remains largely unknown how stromal proliferation versus decidual polyploidization is differentially regulated during decidualization. Utilizing Wnt6-mutant mice, we show here that Wnt6 deficiency impairs stromal cell proliferation without much adverse effects on decidual polyploidization. Applying a primary stromal cell culture model, we further reveal that loss of Wnt6 prolongs the cell cycle length via downregulating cyclin B1 expression, thus attenuating stromal cell proliferation. Our study provides the first genetic evidence that Wnt6 is critical for normal stromal cell proliferation in mice, highlighting the concept that there are differential machineries governing the process of stromal cell proliferation versus decidual transformation during early pregnancy. This finding has high clinical relevance because Wnt signaling is known to be important for human implantation and endometrial function.

Deciphering the molecular basis of uterine receptivity.

Uterine receptivity is defined as a limited time period during which the uterus enters into an appropriately differentiated state that is ready for the initiation of implantation by competent blastocysts. Although various cellular aspects and molecular pathways involved in uterine receptivity have been identified by gene expression studies and genetically engineered mouse models, a comprehensive understanding of the window of uterine receptivity is still missing. This review focuses on the recent progress in this area, with particular focus on the molecular basis of stromal-epithelial dialogue and crosstalk between the blastocyst and the uterus during implantation. A better understanding of the underlying mechanisms governing the window of uterine receptivity is hoped to generate new strategies to correct implantation failure and to improve pregnancy rates in women.

A model for mitotic inheritance of histone lysine methylation.

Histone lysine methylation has been implicated in epigenetic regulation of transcription. Using stable-isotope labelling and quantitative mass spectrometry, we analysed the dynamics of histone lysine methylation. Here we report that histone methylation levels are transiently reduced during S phase and are gradually re-established during subsequent cell cycle stages. However, despite the recovery of overall methylation levels before the next S phase, the methylation levels of parental and newly incorporated histones differ significantly. In addition, histone methylation levels are maintained at steady states by both restriction of methyltransferase activity and the active turnover of methyl groups in cells undergoing an extended G1/S phase arrest. Finally, we propose a 'buffer model' that unifies the imprecise inheritance of histone methylation and the faithful maintenance of underlying gene silencing.

Nucleolar protein Spindlin1 recognizes H3K4 methylation and stimulates the expression of rRNA genes.

The tandem Tudor-like domain-containing protein Spindlin1 has been reported to be a meiotic spindle-associated protein. Here we report that Spindlin1 is not associated with the spindle in mouse embryonic fibroblast cells during mitotic divisions. In interphase cells, Spindlin1 specifically localizes to the nucleoli. Moreover, Spindlin1 is a histone methylation effector protein that specifically recognizes H3K4 methylation. Finally, Spindlin1 localizes to the active ribosomal DNA (rDNA) repeats, and Spindlin1 facilitates the expression of rRNA genes.

[Effect of maternal high fat diet during gestation and lactation period on spatial learning and memory in adult mice offspring].

OBJECTIVE: To investigate the effect of perinatal high fat diet on spatial learning and memory in adult Kunming (KM) mice offspring. METHODS: The adult female KM mice were randomly divided into control and high fat group, fed with lab chow and high fat diet (containing 20% of lard) during gestation and lactation periods. After weaning at 4 weeks old, 10 offspring mice randomly selected from control group, as control continuing (CC) group, were fed with lab chow. 10 mice, as high fat continuing (FF) group, from high fat group were fed with high fat diet. 10 mice, as transforming high fat (FC) group, were fed with lab chow. Then, Morris water maze task was applied to evaluate spatial learning and memory in the pups. The body weight and the mass of visceral fat and brain were weighted, and the level of serum leptin was measured through ELISA. RESULTS: Latency of FF and FC groups were shorter than CC group (P < 0.05), and the crossing times of FC group was more than CC group. The weights, the mass of visceral fat and brain of FF and FC groups were heavier than those of control group (P < 0.05). The level of serum leptin of FF group was higher than CC group (P <0. 05). CONCLUSION: Maternal high fat diet during pregnancy and lactation may contribute to better spatial learning and memory ability in adult mice offspring.

Efficacy of Omega-3 Intake in Managing Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To explore the efficacy of omega-3 fatty acids (FAs) on patients suffering from dry eye disease (DED), a complex inflammatory condition, we reviewed data from PubMed, Embase, ClinicalTrials.gov, Web of Science, and Cochrane CENTRAL in the past 10 years (2013 to 2023). These sources provided randomized clinical trials (RCTs) that examined the efficacy of omega-3 FAs on DED patients with accessible pre- and post-intervention data, excluding trials with overlapping participants, without omega-3 supplementation, or those lacking placebo control or quantitative assessments. Two independent reviewers extracted data related to dry eye symptom scores, tear break-up time (TBUT), Schirmer's tests, osmolarity, and corneal fluorescein staining (CFS), and the results were analyzed by Comprehensive Meta-Analysis software version 4. We incorporated 19 related RCTs assessed by the Cochrane Risk of Bias tool, encompassing 4246 DED patients with various etiologies. Patients given omega-3 treatment demonstrated more significant improvements in dry eye symptoms (Hedges' g = -1.047; p < 0.001), TBUT [standardized mean difference (SMD) = -0.939; p < 0.001], scores from the Schirmer test (SMD = -0.372; p < 0.001), CFS (SMD = -0.299; p = 0.037), and osmolarity (SMD = -0.721; p < 0.001) compared to those on a placebo regimen. In the meta-regression analysis of DED symptoms, the daily dose of omega-3 (coefficient = -0.0005, p = 0.002), duration of omega-3 intake (coefficient = -0.1399, p = 0.021), and percentage of eicosapentaenoic acid (EPA) (coefficient = -0.0154, p < 0.001) exhibited a significant positive correlation with a reduction in dry eye symptom scores. Apart from CFS, similar trends were noted in TBUT, Schirmer tests, and osmolarity scores. Based on the evidence, omega-3 FAs effectively reduce DED symptoms, especially in high doses, for a long duration, and with increased EPA levels. However, given the heterogeneity in study results and diverse patient characteristics, caution is needed in generalizing these findings. In conclusion, omega-3 FA supplementation is still recommended for DED management in clinical settings.

MoJMJD6, a Nuclear Protein, Regulates Conidial Germination and Appressorium Formation at the Early Stage of Pathogenesis in Magnaporthe oryzae.

In plant-pathogen interactions, Magnaporthe oryzae causes blast disease on more than 50 species of 14 monocot plants, including important crops such as rice, millet, and most 15 recently wheat. M. oryzae is a model fungus for studying plant-microbe interaction, and the main source for fungal pathogenesis in the field. Here we report that MoJMJD6 is required for conidium germination and appressorium formation in M. oryzae. We obtained MoJMJD6 mutants (ΔMojmjd6) using a target gene replacement strategy. The MoJMD6 deletion mutants were delayed for conidium germination, glycogen, and lipid droplets utilization and consequently had decreased virulence. In the ΔMojmjd6 null mutants, global histone methyltransferase modifications (H3K4me3, H3K9me3, H3K27me3, and H3K36me2/3) of the genome were unaffected. Taken together, our results indicated that MoJMJD6 function as a nuclear protein which plays an important role in conidium germination and appressorium formation in the M. oryzae. Our work provides insights into MoJMJD6-mediated regulation in the early stage of pathogenesis in plant fungi.

RNAPII Degradation Factor Def1 Is Required for Development, Stress Response, and Full Virulence of Magnaporthe oryzae.

The RNA polymerase II degradation factor Degradation Factor 1 (Def1) is important for DNA damage repair and plays various roles in eukaryotes; however, the biological role in plant pathogenic fungi is still unknown. In this study, we investigated the role of Def1 during the development and infection of the rice blast fungus Magnaporthe oryzae. The deletion mutant of Def1 displayed slower mycelial growth, less conidial production, and abnormal conidial morphology. The appressoria of Δdef1 was impaired in the penetration into host cells, mainly due to blocking in the utilization of conidial storages, such as glycogen and lipid droplets. The invasive growth of the Δdef1 mutant was also retarded and accompanied with the accumulation of reactive oxygen species (ROS) inside the host cells. Furthermore, compared with the wild type, Δdef1 was more sensitive to multiple stresses, such as oxidative stress, high osmotic pressure, and alkaline/acidic pH. Interestingly, we found that Def1 was modified by O-GlcNAcylation at Ser232, which was required for the stability of Def1 and its function in pathogenicity. Taken together, the O-GlcNAc modified Def1 is required for hyphae growth, conidiation, pathogenicity, and stress response in M. oryzae. This study reveals a novel regulatory mechanism of O-GlcNAc-mediated Def1 in plant pathogenic fungi.