Injectable ultrasonic sensor for wireless monitoring of intracranial signals.

Direct and precise monitoring of intracranial physiology holds immense importance in delineating injuries, prognostication and averting disease1. Wired clinical instruments that use percutaneous leads are accurate but are susceptible to infection, patient mobility constraints and potential surgical complications during removal2. Wireless implantable devices provide greater operational freedom but include issues such as limited detection range, poor degradation and difficulty in size reduction in the human body3. Here we present an injectable, bioresorbable and wireless metastructured hydrogel (metagel) sensor for ultrasonic monitoring of intracranial signals. The metagel sensors are cubes 2 × 2 × 2 mm3 in size that encompass both biodegradable and stimulus-responsive hydrogels and periodically aligned air columns with a specific acoustic reflection spectrum. Implanted into intracranial space with a puncture needle, the metagel deforms in response to physiological environmental changes, causing peak frequency shifts of reflected ultrasound waves that can be wirelessly measured by an external ultrasound probe. The metagel sensor can independently detect intracranial pressure, temperature, pH and flow rate, realize a detection depth of 10 cm and almost fully degrade within 18 weeks. Animal experiments on rats and pigs indicate promising multiparametric sensing performances on a par with conventional non-resorbable wired clinical benchmarks.

Orchestrated intron retention regulates normal granulocyte differentiation.

Intron retention (IR) is widely recognized as a consequence of mis-splicing that leads to failed excision of intronic sequences from pre-messenger RNAs. Our bioinformatic analyses of transcriptomic and proteomic data of normal white blood cell differentiation reveal IR as a physiological mechanism of gene expression control. IR regulates the expression of 86 functionally related genes, including those that determine the nuclear shape that is unique to granulocytes. Retention of introns in specific genes is associated with downregulation of splicing factors and higher GC content. IR, conserved between human and mouse, led to reduced mRNA and protein levels by triggering the nonsense-mediated decay (NMD) pathway. In contrast to the prevalent view that NMD is limited to mRNAs encoding aberrant proteins, our data establish that IR coupled with NMD is a conserved mechanism in normal granulopoiesis. Physiological IR may provide an energetically favorable level of dynamic gene expression control prior to sustained gene translation.

Genome-wide transcription factor-binding maps reveal cell-specific changes in the regulatory architecture of human HSPCs.

Hematopoietic stem and progenitor cells (HSPCs) rely on a complex interplay among transcription factors (TFs) to regulate differentiation into mature blood cells. A heptad of TFs (FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, LMO2) bind regulatory elements in bulk CD34+ HSPCs. However, whether specific heptad-TF combinations have distinct roles in regulating hematopoietic differentiation remains unknown. We mapped genome-wide chromatin contacts (HiC, H3K27ac, HiChIP), chromatin modifications (H3K4me3, H3K27ac, H3K27me3) and 10 TF binding profiles (heptad, PU.1, CTCF, STAG2) in HSPC subsets (stem/multipotent progenitors plus common myeloid, granulocyte macrophage, and megakaryocyte erythrocyte progenitors) and found TF occupancy and enhancer-promoter interactions varied significantly across cell types and were associated with cell-type-specific gene expression. Distinct regulatory elements were enriched with specific heptad-TF combinations, including stem-cell-specific elements with ERG, and myeloid- and erythroid-specific elements with combinations of FLI1, RUNX1, GATA2, TAL1, LYL1, and LMO2. Furthermore, heptad-occupied regions in HSPCs were subsequently bound by lineage-defining TFs, including PU.1 and GATA1, suggesting that heptad factors may prime regulatory elements for use in mature cell types. We also found that enhancers with cell-type-specific heptad occupancy shared a common grammar with respect to TF binding motifs, suggesting that combinatorial binding of TF complexes was at least partially regulated by features encoded in DNA sequence motifs. Taken together, this study comprehensively characterizes the gene regulatory landscape in rare subpopulations of human HSPCs. The accompanying data sets should serve as a valuable resource for understanding adult hematopoiesis and a framework for analyzing aberrant regulatory networks in leukemic cells.

The landscape of alterations affecting epigenetic regulators in T-cell acute lymphoblastic leukemia: Roles in leukemogenesis and therapeutic opportunities.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy accounting for 10%-15% of pediatric and 20%-25% of adult ALL cases. Epigenetic irregularities in T-ALL include alterations in both DNA methylation and the post-translational modifications on histones which together play a critical role in the initiation and development of T-ALL. Characterizing the oncogenic mutations that result in these epigenetic changes combined with the reversibility of epigenetic modifications represents an opportunity for the development of epigenetic therapies. Oncogenic mutations and deregulated expression of DNA methyltransferases (DNMTs), Ten-Eleven Translocation dioxygenases (TETs), Histone acetyltransferases (HATs) and members of Polycomb Repressor Complex 2 (PRC2) have all been identified in T-ALL. This review focuses on the current understanding of how these mutations lead to epigenetic changes in T-ALL, their association with disease pathogenesis and the current efforts to exploit these clinically through the development of epigenetic therapies in T-ALL treatment.

A novel cascade allows Metarhizium robertsii to distinguish cuticle and hemocoel microenvironments during infection of insects.

Pathogenic fungi precisely respond to dynamic microenvironments during infection, but the underlying mechanisms are not well understood. The insect pathogenic fungus Metarhizium robertsii is a representative fungus in which to study broad themes of fungal pathogenicity as it resembles some major plant and mammalian pathogenic fungi in its pathogenesis. Here we report on a novel cascade that regulates response of M. robertsii to 2 distinct microenvironments during its pathogenesis. On the insect cuticle, the transcription factor COH2 activates expression of cuticle penetration genes. In the hemocoel, the protein COH1 is expressed due to the reduction in epigenetic repression conferred by the histone deacetylase HDAC1 and the histone 3 acetyltransferase HAT1. COH1 interacts with COH2 to reduce COH2 stability, and this down-regulates cuticle penetration genes and up-regulates genes for hemocoel colonization. Our work significantly advances the insights into fungal pathogenicity in insects.

Graph Convolutional Network-Enhanced Model for Screening Persistent, Mobile, and Toxic and Very Persistent and Very Mobile Substances.

The global management for persistent, mobile, and toxic (PMT) and very persistent and very mobile (vPvM) substances has been further strengthened with the rapid increase of emerging contaminants. The development of a ready-to-use and publicly available tool for the high-throughput screening of PMT/vPvM substances is thus urgently needed. However, the current model building with the coupling of conventional algorithms, small-scale data set, and simplistic features hinders the development of a robust model for screening PMT/vPvM with wide application domains. Here, we construct a graph convolutional network (GCN)-enhanced model with feature fusion of a molecular graph and molecular descriptors to effectively utilize the significant correlation between critical descriptors and PMT/vPvM substances. The model is built with 213,084 substances following the latest PMT classification criteria. The application domains of the GCN-enhanced model assessed by kernel density estimation demonstrate the high suitability for high-throughput screening PMT/vPvM substances with both a high accuracy rate (86.6%) and a low false-negative rate (6.8%). An online server named PMT/vPvM profiler is further developed with a user-friendly web interface (http://www.pmt.zj.cn/). Our study facilitates a more efficient evaluation of PMT/vPvM substances with a globally accessible screening platform.

Paternal and maternal exposures to adverse childhood experiences and spontaneous fetal loss: a nationwide cross-sectional analysis.

BACKGROUND: Adverse childhood experiences (ACEs) might be associated with maternal spontaneous fetal loss, while evidence among Chinese population is limited. This study aims to explore the associations of adverse childhood experiences (ACEs) among women and their spouses with the risk of spontaneous abortion and stillbirth. METHOD: Data were from the China Health and Retirement Longitudinal Study (CHARLS) 2014 survey. ACEs were categorized into intra-familial ACEs and extra-familial ACEs. The associations of maternal and paternal ACEs with women's history of spontaneous abortion and stillbirth were investigated by logistic regression. RESULTS: 7,742 women were included with 9.05% and 2.47% experiencing at least one spontaneous abortion or stillbirth, respectively. Women exposed to 2, 3, and ≥ 4 ACEs were at significantly higher odds of spontaneous abortion, with adjusted odds ratios (ORs) of 1.52 (95% [CI, Confidence Interval] 1.10-2.10), 1.50 (95% CI 1.07-2.09) and 1.68 (95% CI 1.21-2.32), respectively. A significant association between ≥ 4 maternal intra-familial ACEs and stillbirth (OR 2.23, 95% CI 1.12-4.42) was also revealed. Furthermore, paternal exposures to 3 and ≥ 4 overall ACEs were significantly associated with their wives' history of spontaneous abortion, with adjusted ORs of 1.81 (95% CI 1.01-3.26) and 1.83 (95% CI 1.03-3.25), respectively. CONCLUSION: Both maternal and paternal ACEs were associated with spontaneous abortion, and potential mediators might need to be considered to further explore impacts of maternal and paternal ACEs on maternal reproductive health.

Dexmedetomidine nasal administration improves perioperative sleep quality and neurocognitive deficits in elderly patients undergoing general anesthesia.

OBJECTIVE: To investigate the improvement of perioperative sleep quality and neurocognitive impairment in elderly patients under general anesthesia by nasal administration of dexmedetomidine. METHODS: One hundred and twenty patients admitted to our hospital for various laparoscopic elective gynecological surgeries lasting more than 1 h under general anesthesia from July 2021 to March 2023 were selected. All subjects were divided into 3 groups according to the random number table method. From 21:00 to 21:30 every night from one day before to 5 days after surgery, group A was given alprazolam 0.4 mg orally; group B was given dexmedetomidine 1.5ug/kg nasal drip; group C was given saline nasal drip. All subjects were observed for general information, sleep quality, postoperative cognitive function, anxiety status, sleep quality, adverse effects and complication occurrence. RESULTS: The difference in general information between the three groups was not statistically significant, P > 0.05; the sleep quality scores of the three groups on admission were not statistically significant, P > 0.05. At the Preoperative 1d, postoperative 1d, 3d and 5d, the RCSQ scores of the subjects in group A and group B were higher than those in groups C, and with the postoperative RCSQ scores of subjects in group B were higher as the time increased; the assessment of anxiety status in the three groups 1d before surgery was not statistically significant, P > 0.05. The cognitive function scores of subjects in the three groups were not statistically significant in the preoperative 1d, P > 0.05. The postoperative 1d (24.63 ± 2.23), 3d (25.83 ± 2.53), and 5d (26.15 ± 2.01) scores of the subjects in group B were higher than those in groups A and C (P < 0.05), and the subjects in group B had better recovery of postoperative cognitive function with increasing time; the occurrence of postoperative delirium (POD) in group B (12.5%) were lower on postoperative 5d than those in groups A (37.5%) and C (32.5%) (P < 0.05). There was no statistical significance in the evaluation of anxiety state of the three groups on the first day before operation (P > 0.05). The scores in group B were lower than those in group C on the postoperative 1d, 3d, 5 d (P < 0.05). The overall incidence of adverse reactions and complications in subjects in group B was 17.5% significantly lower than that in groups A and C (P < 0.05). CONCLUSION: Dexmedetomidine can effectively improve the sleep disorder of elderly general anesthesia patients, reduce the damage to their neurocognitive function and the occurrence of POD, effectively reduce the anxiety of patients and the occurrence of adverse reactions and complications, and has better sedative, improve postoperative cognitive function and anti-anxiety effects, with a high drug safety, worthy of clinical application and promotion.

Salvage Latarjet may provide worse outcomes in terms of recurrent instability and returning to sports compared to primary Latarjet: a systematic review of comparative studies.

BACKGROUND: The Latarjet procedure (LP) is performed as a primary stabilization procedure (primary LP) and a salvage procedure when an earlier shoulder stabilization procedure has failed (salvage LP). However, whether primary LP or salvage LP provides better outcomes for anterior shoulder instability remains unknown. METHODS: Two independent reviewers performed the literature search based on the PRISMA guidelines. A comprehensive search of PubMed, Embase, web of science and Cochrane Library was performed from their inception date to December 4, 2023. Inclusion criteria mainly included the comparison of postoperative outcomes between primary and salvage LP, English language, and full text availability. Two reviewers independently examined the literature, collected data, and evaluated the methodological robustness of the included studies. The Methodological Index for Nonrandomized Studies was used to evaluate the quality of nonrandomized studies. Recurrent instability, complications, reoperations, return to sports, patient-reported outcomes, and range of motion were assessed. Statistical evaluations were conducted using Manager V.5.4.1 (The Cochrane Collaboration, Software Update, Oxford, UK). RESULTS: Twelve studies were included in the systematic review, with 940 shoulders undergoing primary LP and 631 shoulders undergoing salvage LP. Statistically significant differences in favor of primary LP were found in 2 of the 11 and 2 of 4 included studies in terms of recurrent instability and returning to the same sports (RTS) at preinjury level, respectively. In terms of the visual analog scale, subjective shoulder value and the Western Ontario Shoulder Instability Index, 2 of the 4, 1 of the 3 and 1 of the 3 included studies reported statistically significant differences in favor of primary LP. Differences were not noticed regarding complications, reoperations, the time to RTS, the Rowe score, the Athletic Shoulder Outcome Scoring System, and forward flexion. CONCLUSION: Current evidence suggests that compared with primary LP, salvage LP may provide inferior postoperative outcomes in terms of recurrent instability and the rate of RTS at preinjury level. Primary and salvage LP may yield comparable efficacy in terms of complications, reoperations, the rate of RTS, the time to RTS, pain, shoulder function, and range of motion. PROSPERO ID: CRD42023492027.

Lower Reoperation Rate and Superior Patient-reported Outcome Following Arthroscopic Rotator Cuff Repair with Concomitant Acromioplasty: An Updated Systematic Review of Randomized Controlled Trials.

PURPOSE: This study aims to systematically assess the postoperative outcomes in patients undergoing arthroscopic rotator cuff repairs with or without concomitant acromioplasty through a rigorous systematic review of randomized controlled trial s (RCTs). METHODS: This systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, aimed to identify RCTs comparing clinical outcomes of patients with full thickness rotator cuff tears undergoing arthroscopic rotator cuff repair with acromioplasty versus those without at a minimum of 12 months follow-up. Databases searched included PubMed, Web of Science, Embase, and the Cochrane Library. The risk of bias in the included studies was assessed using the revised Cochrane Risk of Bias 2 (RoB2). Meta-analysis was conducted for outcomes with at least three studies reporting, with pooled effect estimates calculated using either fixed-effect or random-effects models based on heterogeneity levels. Results were presented as the weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CIs). For outcomes with fewer than three studies reporting, a Fisher exact test was conducted, with continuity correction applied if necessary. Primary outcomes include rates of retear and reoperation, while secondary outcomes included improvement in American Shoulder and Elbow Surgeons (ASES) score, range of motion (ROM), and complication rate. RESULTS: Five high-quality RCTs, with low bias risk, involving 409 patients, revealed demographics of 58.4% males, mean age 58.4 years, and acromion types: 12.2% type I, 70.7% type II, and 17.1% type III. Mean follow-up was 52.2 months. Retear (12.5% versus 16.1%, P = 0.536) and complication rates (OR, 3.11; 95% CI, 0.31-30.73; P=0.33) were comparable between the two groups. However, reoperation rate (5.3% versus 15.9%, P < 0.001) and improvement in ASES score (WMD, 3.99; 95% CI, 1.00-6.99; P=0.009) favored the acromioplasty group. Both groups showed significant improvements in ROM, but insufficient data prevented a comparison. CONCLUSIONS: Compared to arthroscopic rotator cuff repair alone, arthroscopic rotator cuff repair with acromioplasty demonstrated similar rates of retear and complications, but a significantly lower reoperation rate and superior improvement in ASES score. The available data were insufficient to draw a definitive conclusion regarding ROM. This conclusion is fragile due to a limited sample size.

Disruption of a GATA2-TAL1-ERG regulatory circuit promotes erythroid transition in healthy and leukemic stem cells.

Changes in gene regulation and expression govern orderly transitions from hematopoietic stem cells to terminally differentiated blood cell types. These transitions are disrupted during leukemic transformation, but knowledge of the gene regulatory changes underpinning this process is elusive. We hypothesized that identifying core gene regulatory networks in healthy hematopoietic and leukemic cells could provide insights into network alterations that perturb cell state transitions. A heptad of transcription factors (LYL1, TAL1, LMO2, FLI1, ERG, GATA2, and RUNX1) bind key hematopoietic genes in human CD34+ hematopoietic stem and progenitor cells (HSPCs) and have prognostic significance in acute myeloid leukemia (AML). These factors also form a densely interconnected circuit by binding combinatorially at their own, and each other's, regulatory elements. However, their mutual regulation during normal hematopoiesis and in AML cells, and how perturbation of their expression levels influences cell fate decisions remains unclear. In this study, we integrated bulk and single-cell data and found that the fully connected heptad circuit identified in healthy HSPCs persists, with only minor alterations in AML, and that chromatin accessibility at key heptad regulatory elements was predictive of cell identity in both healthy progenitors and leukemic cells. The heptad factors GATA2, TAL1, and ERG formed an integrated subcircuit that regulates stem cell-to-erythroid transition in both healthy and leukemic cells. Components of this triad could be manipulated to facilitate erythroid transition providing a proof of concept that such regulatory circuits can be harnessed to promote specific cell-type transitions and overcome dysregulated hematopoiesis.

Increased amplitude of subendometrial contractions identified by ultrasound speckle tracking in women with a caesarean scar defect.

RESEARCH QUESTION: What is the effect of a caesarean scar defect on subendometrial contractions? DESIGN: Prospective cohort study in a Dutch medical centre including women with a niche in the uterine caesarean section scar. Data were compared with controls without a caesarean section scar. All women underwent a 5-min recording by transvaginal ultrasound at four phases in the menstrual cycle: during menses; late follicular; early luteal; or late luteal phase. Uterine motion analysis was evaluated by dedicated speckle tracking using two-dimensional optical flow. MAIN OUTCOME: amplitude of the subendometrial contractions. RESULTS: Thirty-one women with a niche in the uterine scar and 11 controls, matched for menstrual cycle phase, were included. The amplitude of the subendometrial contractions was significantly higher in women with a niche compared with controls during all phases of the menstrual cycle (menses P < 0.001; late follicular P < 0.001; early luteal P = 0.028; late luteal P = 0.003). Velocity was lower in women with a niche during late follicular phase only (P = 0.012). A positive correlation between niche sizes (depth, length) and amplitude of subendometrial contractions was found. CONCLUSION: Subendometrial contractions were affected in women with a niche in the caesarean section scar compared with women who had not undergone a previous caesarean section. Contraction amplitude was higher and independent of the menstrual phase. These findings may cause postmenstrual spotting, dysmenorrhoea and lower implantation rates in women with a niche. Future studies should investigate this association and the underlying pathways.

Uterine contractile activity in healthy women throughout the menstrual cycle measured using a novel quantitative two-dimensional transvaginal ultrasound speckle tracking method.

RESEARCH QUESTION: To explore normal uterine contractile function across the menstrual cycle using a novel quantitative ultrasound method. DESIGN: This multicentre prospective observational study took place in three European centres from 2014 to 2022. Uterine contraction frequency (contractions/minute), amplitude, direction (cervix-to-fundus, C2F; fundus-to-cervix; F2C), velocity and coordination were investigated. Features were extracted from transvaginal ultrasound recordings (TVUS) using speckle tracking. Premenopausal women ≥18 years of age, with normal, natural menstrual cycles were included. A normal cycle was defined as: regular (duration 28 ± 2 days), no dysmenorrhoea, no menometrorrhagia. Four-minute TVUS were performed during the menstrual phase, mid-follicular, late follicular phase, early luteal phase and/or late luteal phase. Of the 96 recordings available from 64 women, 70 were suitable for inclusion in the analysis. RESULTS: Contraction frequency (for the posterior wall) and velocity (for the anterior uterine wall in the F2C direction) were highest in the late follicular phase and lowest in the menstrual and late luteal phases (1.61 versus 1.31 and 1.35 contractions/min, P < 0.001 and 0.81 versus 0.67 and 0.62 mm/s, P < 0.001, respectively). No significant difference was found for contraction amplitude. Contraction coordination (simultaneous contraction of the anterior and posterior walls in the same direction) was least coordinated in the mid-follicular phase (P = 0.002). CONCLUSIONS: This is the first study to objectively measure uterine contraction features in healthy women during the natural menstrual cycle on TVUS. Likewise, it introduces contraction coordination as a specific feature of uterine peristalsis. Differences in uterine contractility across the menstrual cycle are confirmed, with highest activity seen in the late follicular phase, and lowest in the late luteal phase.

Effects of dietary soluble ß-1,3-glucan on the growth performance, antioxidant status, and immune response of the river prawn (Macrobrachium nipponense).

The effects of dietary ß-1,3-glucan on the growth performance, body composition, hepatopancreas tissue structure, antioxidant activities, and immune response of the river prawn (Macrobrachium nipponense) were investigated. In total, 900 juvenile prawns were fed one of five diets with different contents of ß-1,3-glucan (0%, 0.1%, 0.2%, and 1.0%) or 0.2% curdlan for 6 weeks. The growth rate, weight gain rate, specific growth rate, specific weight gain rate, condition factor, and hepatosomatic index of juvenile prawns fed 0.2% ß-1,3-glucan were significantly higher than those fed 0% ß-1,3-glucan and 0.2% curdlan (p < 0.05). The whole-body crude lipid content of prawns supplemented with curdlan and ß-1,3-glucan was significantly higher than that of the control group (p < 0.05). The antioxidant and immune enzyme activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT), lysozyme (LZM), phenoloxidase (PO), acid phosphatase (ACP), and alkaline phosphatase (AKP) in the hepatopancreas of juvenile prawns fed 0.2% ß-1,3-glucan were significantly higher than those of the control and 0.2% curdlan groups (p < 0.05), and tended to increase and then decrease with increasing dietary ß-1,3-glucan. The highest malondialdehyde (MDA) content was observed in juvenile prawns without ß-1,3-glucan supplementation. The results of real-time quantitative PCR indicated that dietary ß-1,3-glucan promoted expression of antioxidant and immune-related genes. Binomial fit analysis of weight gain rate and specific weight gain rate showed that the optimum ß-1,3-glucan requirement of juvenile prawns was 0.550%-0.553%. We found that suitable dietary ß-1,3-glucan improved juvenile prawns growth performance, antioxidant capacity, and non-specific immunity, which provide reference for shrimp healthy culture.

Dietary melatonin positively impacts the immune system of crayfish, Cherax destructor, as revealed by comparative proteomics analysis.

Melatonin, an indoleamine with various biological activities, is being used increasingly in the aquaculture industry for its broad immune effects. Cherax destructor is an emerging economically cultured crayfish that faces many problems in the breeding process. Previous work found that dietary melatonin has positive effects on the growth and immunity of C. destructor, but the specific mechanism involved remained unclear. In this study, proteomics was used to determine the mechanism of action of melatonin in C. destructor. Results showed that dietary melatonin resulted in decreased levels of hydrogen peroxide, alanine aminotransferase, and aspartate aminotransferase, but increased levels of glutathione peroxidase, acid phosphatase, and glutathione S-transferases. In total, 608 proteins were differentially expressed (418 upregulated and 190 downregulated), and were enriched in three main categories: innate immunity (B cell receptor signaling pathway and natural killer cell-mediated cytotoxicity), glucose metabolism (pentose phosphate pathway, pentose and glucuronate interconversions, and propionate metabolism), and amino acid metabolism (valine, leucine, and isoleucine degradation, and cysteine and methionine metabolism). In addition, dietary melatonin was also involved in the regulation of the mTOR signaling pathway, and upregulated the expression of genes encoding key factors, such as Ras-related GTP-binding protein A/B, eukaryotic initiation factor 4E, eukaryotic initiation factor 4E-binding protein, and p70 ribosomal S6 kinase. Overall, this study demonstrates the role of melatonin in the physiological regulation of C. destructor, laying the foundation for the development of melatonin as a feed additive in the aquaculture of this species.

Effects of ß-1,3-glucan on growth, immune responses, and intestinal microflora of the river prawn (Macrobrachium nipponense) and its resistance against Vibrio parahaemolyticus.

In this study, we investigated the impact of ß-1,3-glucan on the immune responses and gut microbiota of the river prawn (Macrobrachium nipponense) in the presence of Vibrio parahaemolyticus stress. Shrimps were fed one of the following diets: control (G1), 0.2% curdlan (G2), 0.1% ß-1,3-glucan (G3), 0.2% ß-1,3-glucan (G4), or 1.0% ß-1,3-glucan (G5) for 6 weeks and then challenged with V. parahaemolyticus for 96 h. Under Vibrio stress, shrimps in G4 exhibited the highest length gain rate, weight gain rate, and survival rate. They also showed increased intestinal muscle thickness and villus thickness compared to the control and 0.2% curdlan groups. The apoptosis rate was lower in G4 than in the control group, and the digestive enzyme activities (pepsin, trypsin, amylase, and lipase), immune enzyme activities (acid phosphatase, alkaline phosphatase, lysozyme, and phenoxidase), and energy metabolism (triglyceride, cholesterol, glycogen, and lactate dehydrogenase) were enhanced. Expression levels of growth-related genes (ecdysone receptor, calmodulin-dependent protein kinase I, chitin synthase, and retinoid X receptor) and immune-related genes (toll-like receptor 3, myeloid differentiation primary response 88, mitogen-activated protein kinase 7, and mitogen-activated protein kinase 14) were higher in G4 than in the control. Microbiota analysis indicated higher bacterial abundance in shrimps fed ß-1,3-glucan, as evidenced by Sob, Chao1, and ACE indices. Moreover, 0.2% ß-1,3-glucan increased the relative abundances of Bacteroidota and Firmicutes while reducing those of Corynebacteriales and Lactobacillales. In summary, ß-1,3-glucan enhances immune enzyme activities, alters immune-related gene expression, and impacts gut microbial diversity in shrimp. These findings provide valuable insights into the mechanisms underlying ß-1,3 glucan's immune-enhancing effects.

Embryonic Exposure to UV-328 Impairs the Cell Cycle in Zebrafish (Danio rerio) by Inhibiting the p38 MAPK/p53/Gadd45a Signaling Pathway.

The benzotriazole UV stabilizer UV-328 is well known for its potent antioxidative properties; however, there are concerns about how it may affect signaling nodes and lead to negative consequences. This study identified the key signaling cascades involved in oxidative stress in zebrafish (Danio rerio) larvae and evaluated the cell cycle arrests and associated developmental alternations. Exposure to UV-328 at 0.25, 0.50, 1.00, 2.00, and 4.00 µg/L downregulated gene expression associated with oxidative stress (cat, gpx, gst, and sod) and apoptosis (caspase-3, caspase-6, caspase-8, and caspase-9) at 3 days postfertilization (dpf). The transcriptome aberration in zebrafish with disrupted p38 mitogen-activated protein kinase (MAPK) cascades was validated based on decreased mRNA expressions of p38 MAPK (0.36-fold), p53 (0.33-fold), and growth arrest and DNA damage-inducible protein 45 α (Gadd45a) (0.52-fold) after a 3- and 14-day exposure alongside a correspondingly decreased protein expression. The percentage of cells in the Gap 1 (G1) phase increased from 69.60% to a maximum of 77.07% (p < 0.05) in the 3 dpf embryos. UV-328 inhibited the p38 MAPK/p53/Gadd45a regulatory circuit but promoted G1 phase cell cycle arrest, abnormally accelerating the embryo hatching and heart rate. This study provided mechanistic insights that enrich the risk profiles of UV-328.

Angiogenic Activity and Mechanism for Bisphenols on Endothelial Cell and Mouse: Evidence of a Structural-Selective Effect.

Increased epidemiological evidence indicates the association of bisphenol exposure with human vascular disorders, while the underlying mechanism has not been clarified. Here, we sought to unveil the potential angiogenic effect and the underlying mechanism of bisphenols with different structural features using endothelial cells treated with an environmentally relevant concentration of bisphenols (range: 1 nM to 10 µM) and a C57BL/6 mouse model fed with doses of 0.002, 0.02, 2, and 20 mg/kg BW/day for 5 weeks. Bisphenol A (BPA) and bisphenol S (BPS) at a 1 nM level significantly increased tube formation by 45.1 and 30.2% and induced the microvessel sprouting, while tube length and microvessel sprouting were significantly inhibited by 37.2 and 55.7% after exposure to tetrabromobisphenol S (TBBPS) at 1 µM, respectively. Mechanistically, TBBPA and TBBPS significantly inhibited the interaction between phosphatidylinositol 3-kinase (PI3K) and thyroid receptor (TR), while BPA and BPS favored the interaction between PI3K and estrogen receptor (ER), resulting in abnormal PI3K signaling with consequent distinct angiogenic activity. BPA- and BPS-induced pro-angiogenic effects and TBBPS showed anti-angiogenic effects due to their distinct disruption on the TR/ER-PI3K pathway. Our work provided new evidence and mechanistic insight on the angiogenic activity of bisphenols and expanded the scope of endocrine disruptors with interference in vascular homeostasis.

Clinical observation of menopause hormone therapy in postmenopausal women with euthyroid and mild subclinical hypothyroidism.

BACKGROUND: To evaluate the endocrine hormone and metabolic indices in postmenopausal women with euthyroid and mild subclinical hypothyroidism after menopause hormone therapy (MHT). METHODS: A retrospective study of 587 postmenopausal women receiving MHT was conducted. Median (25-75th percentile) age was 52 (49-54) years. According to thyroid stimulating hormone (TSH) levels at initial diagnosis, the patients were divided into three groups: I (euthyroid with low normal TSH range, n = 460), II (euthyroid with upper normal TSH range, n = 106) and III (mild subclinical hypothyroidism, n = 21). After a continuous oral MHT regimen using the same estradiol potency for 6-18 month cycles, serum endocrine hormone and metabolic indices were reassessed. RESULTS: Compared with baseline, serum TSH levels in groups I and II significantly changed but all values were within the normal range. No significant difference was observed in serum TSH levels in group III. After treatment, all serum free tri-iodothyronine and free thyroxine levels were within the normal range. Serum total cholesterol, triglyceride, fasting plasma glucose, fasting insulin levels and homeostasis model assessment of insulin resistance index had significantly decreased in group I. There were no significant differences in all observed lipid and glucose parameters in group III, before and after treatment. CONCLUSION: MHT did not affect thyroid function in postmenopausal women with euthyroid and mild subclinical hypothyroidism. MHT led to an improvement in lipid and glucose indicators in euthyroid women with low normal TSH range.

Development and validation of a predictive model of abnormal uterine bleeding associated with ovulatory dysfunction: a case-control study.

BACKGROUND: Abnormal uterine bleeding associated with ovulatory dysfunction (AUB-O) is a typical gynecological disease that can affect women of various ages. Being able to identify women at risk of AUB-O could allow physicians to take timely action. This study aimed to identify the influencing factors of AUB-O in Chinese women, and then develop and validate a predictive model. METHODS: In this multicenter case-control study, 391 women with AUB-O and 838 controls who came from nine hospitals in Zhejiang province were recruited between April 2019 and January 2022. All the participants completed a structured questionnaire including general characteristics, lifestyle and habits, menstrual and reproductive history, and previous diseases. The predictive model was developed on a group of 822 women and validated on a group of 407 women. Logistic regression was adopted to investigate the influencing factors and develop the model, and validation was then performed. RESULTS: The independent predictive factors of AUB-O were age (OR 1.073, 95% CI 1.046-1.102, P < 0.001), body mass index (OR 1.081, 95% CI 1.016-1.151, P = 0.015), systolic blood pressure (OR 1.016, 95% CI 1.002-1.029, P = 0.023), residence (OR 2.451, 95% CI 1.727-3.478, P < 0.001), plant-based diet (OR 2.306, 95% CI 1.415-3.759, P < 0.001), fruits eating (OR 1.887, 95% CI 1.282-2.776, P = 0.001), daily sleep duration (OR 0.819; 95% CI 0.708-0.946, P = 0.007), multiparous (parity = 1, OR 0.424, 95% CI 0.239-0.752, P = 0.003; parity > 1, OR 0.450, 95% CI 0.247-0.822, P = 0.009), and history of ovarian cyst (OR 1.880, 95% CI 1.305-2.710, P < 0.001). The predictive ability (area under the curve) in the development group was 0.77 (95% CI 0.74-0.81), while in the validation group it was 0.73 (95% CI 0.67-0.79). The calibration curve was in high coincidence with the standard curve in the development group, and similar to the validation group. A tool for AUB-O risk calculation was created. CONCLUSIONS: Nine influencing factors and a predictive model were proposed in this study, which could identify women who are at high risk of developing AUB-O. This finding highlights the importance of early screening and the lifelong management of ovulatory disorders for women.