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Protein acetylation is a common and reversible posttranslational modification tightly governed by protein acetyltransferases and deacetylases crucial for various biological processes in both eukaryotes and prokaryotes. Although recent studies have characterized many acetyltransferases in diverse bacterial species, only a few protein deacetylases have been identified in prokaryotes, perhaps in part due to their limited sequence homology. In this study, we identified YkuR, encoded by smu_318, as a unique protein deacetylase in Streptococcus mutans. Through protein acetylome analysis, we demonstrated that the deletion of ykuR significantly upregulated protein acetylation levels, affecting key enzymes in translation processes and metabolic pathways, including starch and sucrose metabolism, glycolysis/gluconeogenesis, and biofilm formation. In particular, YkuR modulated extracellular polysaccharide synthesis and biofilm formation through the direct deacetylation of glucosyltransferases (Gtfs) in the presence of NAD+. Intriguingly, YkuR can be acetylated in a nonenzymatic manner, which then negatively regulated its deacetylase activity, suggesting the presence of a self-regulatory mechanism. Moreover, in vivo studies further demonstrated that the deletion of ykuR attenuated the cariogenicity of S. mutans in the rat caries model, substantiating its involvement in the pathogenesis of dental caries. Therefore, our study revealed a unique regulatory mechanism mediated by YkuR through protein deacetylation that regulates the physiology and pathogenicity of S. mutans.

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Over the years, CAR-T cell therapy has achieved remarkable success in treating hematological malignancies. However, this efficacy has not been replicated in the context of glioblastoma (GBM). In this study, a PD1CD28 chimeric molecule was introduced into EGFRvⅢ-directed CAR-T cells, generating EGFRvⅢ-P2A-PD1CD28 CAR-T cells. Notably, this modification significantly increased IL-2 secretion and enhanced antigen-dependent activation of CAR-T cells, especially when programmed cell death ligand 1 (PD-L1) was present in vitro. In addition, the in vivo xenograft experiments revealed that the PD1CD28 chimeric molecule played a pivotal role in reducing recurrence rates, effectively controlling recurrent tumor volume, and ultimately prolonging the survival of mice. Collectively, these findings suggest that EGFRvⅢ-directed CAR-T cells co-expressing the PD1CD28 chimeric molecule have the potential to significantly enhance the treatment efficacy against GBM.

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Currently, surgery remains the primary treatment for craniocerebral tumors. Before doctors perform surgeries, they need to determine the surgical plan according to the shape, location, and size of the tumor; however, various conditions of different patients make the tumor segmentation task challenging. To improve the accuracy of determining tumor shape and realizing edge segmentation, a U-shaped network combining a residual pyramid module and a dual feature attention module is proposed. The residual pyramid module can enlarge the receptive field, extract multiscale features, and fuse original information, which solves the problem caused by the feature pyramid pooling where the local information is not related to the remote information. In addition, the dual feature attention module is proposed to replace the skip connection in the original U-Net network, enrich the features, and improve the attention of the model to space and channel features with large amounts of information to be used for more accurate brain tumor segmentation. To evaluate the performance of the proposed model, experiments were conducted on the public datasets Kaggle_3M and BraTS2021. Because the model proposed in this study is applicable to two-dimensional image segmentation, it is necessary to obtain the crosscutting images of fair class in the BraTS2021 dataset in advance. Results show that the model accuracy, Jaccard similarity coefficient, Dice similarity coefficient, and false negative rate (FNR) on the Kaggle_3M dataset are 0.9395, 0.8812, 0.8958, and 0.007, respectively. The model accuracy, Jaccard similarity coefficient, Dice similarity coefficient, and FNR on the BraTS2021 dataset were 0.9375, 0.9072, 0.8981, and 0.0087, respectively. Compared with existing algorithms, all the indicators of the proposed algorithm have been improved, but the proposed model still has certain limitations and has not been applied to actual clinical trials. For specific datasets, the generalization ability of the model needs to be further improved. In the future work, the model will be further improved to address the aforementioned limitations.

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Introduction: Reactive oxygen species (ROS) generation is a common disease defense mechanism in plants. However, it is unclear whether Citrus host activates defense response against Diaporthe citri causing citrus melanose disease by producing ROS, and the underlying molecular mechanisms are unknown. Methods: DAB staining and RNA-Seq technology were used to compare the active oxygen burst and differential gene expression, respectively, in uninfected and infected Citrus sinensis leaves at different time points during D. citri infection in vivo. The functions of CsRBOH (a significant DEG) were confirmed in N. benthamiana through the Agrobacterium-mediated transient expression system. Results: DAB staining indicated that C. sinensis initiated defense against D. citri infection within 24 h by generating ROS. Illumina sequencing revealed 25,557 expressed genes of C. sinensis. The most upregulated DEGs (n = 1,570) were identified 72 h after fungal inoculation (sample denoted as CD72). In the CD72 vs. Cs (samples at 0 h after fungal inoculation) comparison, the KEGG pathway category with the highest number of genes (n = 62) and most significant enrichment was Protein processing in endoplasmic reticulum, followed by Glutathione metabolism and MAPK signaling pathway-plant. GO analysis revealed that the DEGs of CD72 vs. Cs related to active oxygen burst and chitin recognition were significantly grouped into the regulation of biological processes and molecular functions, with GO terms including response to ROS, response to fungus, and oxidoreductase activity. Remarkably, CsRBOH was significantly enriched in the GO and KEGG analyses, and its expression pattern in qRT-PCR and DAB staining results were consistent. Among the 63 ROS-related DEGs, HSP genes and genes associated with the peroxidase family were highly significant as revealed by protein-protein interaction networks. Furthermore, ROS accumulation, cell death, and upregulation of defense-related genes were observed in N. benthamiana leaves with CsRBOH expressed through the Agrobacterium-mediated transient expression system. Conclusion: Our findings suggested that C. sinensis activates CsRBOH and ROS-related genes, leading to ROS accumulation to resist the invasion by D. citri. This study laid the foundation for future research on molecular mechanisms and breeding of C. sinensis cultivars resistant to citrus melanose.

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Achieving stable and high-rate partial nitrification (PN) remains a worldwide technical conundrum in low-strength mainstream conditions. This study successfully achieved ultrarapid mainstream PN within 8 days under a saturated dissolved oxygen (DO) supply strategy, reaching a record-breaking PN rate of over 1.0 kg N m-3 d-1 treating municipal wastewater. Stable PN was maintained for over 200 days with an ultrahigh nitrite accumulation ratio of 98.5 ±â€¯0.9 %, resilient to seasonal fluctuations in temperature (16.0-25.6 °C) and load (NH4+-N, 40-80 mg N/L). Kinetics revealed a remarkable 159.1-fold increase in the maximum activity ratio of ammonia-oxidizing bacteria (AOB) to nitrite-oxidizing bacteria (NOB). The faster response of AOB to saturated DO stimulated its highest activity difference with NOB, contributing to the AOB (Nitrosomonas oligotropha) boom and the elimination of NOB groups (-99.9 %). Our results highlight the importance of promoting AOB rather than solely focusing on NOB suppression for initiating and stabilizing high-rate mainstream PN.

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The quick and accurate measurement and evaluation of the deterioration degree and consolidation effectiveness on the surface of masonry relics is valuable for disease investigation and restoration work. However, there is still a lack of quantitative indices for evaluating the deterioration degree and consolidation effectiveness of masonry relics in situ. Based on the micro-drilling resistance method, new quantitative evaluation indices for the deterioration degree and consolidation of masonry materials were proposed. Five types of masonry samples with different deterioration degrees were prepared by artificially accelerated deterioration tests involving sandstone and clay brick as research objects. Three types of consolidants were used to consolidate the deteriorated samples. Drilling resistance tests were conducted for deteriorated and consolidated samples. The variations in deterioration depth and average drilling resistance for samples with different numbers of deterioration cycles were analysed, while the differences in consolidation depth and average drilling resistance for samples with different consolidant types and dosages were compared. Finally, the deterioration degree index ( K ) and consolidation effectiveness index ( R c ), which are based on the average drilling resistance, are proposed. The results can be applied to quick on-site investigations of immovable masonry relics.

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Humans have a limited amount of cognitive resources to process various cognitive operations at a given moment. The Source of Activation Confusion model of episodic memory proposes that resources are consumed during each processing, and once depleted, they need time to recover gradually. This has been supported by a series of behavioral findings in the past. However, the neural substrate of the resources is not known. In the present study, over an existing electroencephalogram data set of a free recall task (Kahana et al., 2022), we provided a neural index reflecting the amount of cognitive resources available for forming new memory traces. Unique to our approach, we obtained the neural index not through correlating neural patterns with behavior outcomes or experimental conditions, but by demonstrating its alignment with a latent quantity of cognitive resources inferred from the Source of Activation Confusion model. In addition, we showed that the identified neural index can be used to propose novel hypothesis regarding other long-term memory phenomena. Specifically, we found that according to the neural index, neural encoding patterns for subsequently recalled items correspond to greater available cognitive resources compared with those for subsequently unrecalled items. This provides a mechanistic account for the long-established subsequent memory effects (i.e., differential neural encoding patterns between subsequently recalled vs. subsequently unrecalled items), which has been previously associated with attention, fatigue, and properties of the stimuli. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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OBJECTIVES: To gain a deeper understanding of the real experiences and needs of the patients of Peutz-Jeghers syndrome (PJS) with fertility concerns. DESIGN: A qualitative study. METHODS: Phenomenological research and Semi-structured method were conducted with the patients of PJS (N = 16), and the interview data were analyzed using inductive content analysis strategies. RESULTS: 16 patients were interviewed, including 13 women and 3 men partners. We identified 5 themes, including: (i) Heritability of disease, (ii) Potential risks of reproduction; (iii) The difficulties in raising children; (iv) family and social support. (V) Need support from multiple sources. CONCLUSION: The findings of this study demonstrate that patients with Peutz-Jeghers syndrome (PJS) who are of childbearing age experience various reproductive concerns and other manifestations. Therefore, it is essential to offer individualized psychological interventions for PJS patients at different psychological stages, with the support of healthcare professionals, family, and social networks.

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Air pollutants combined with Hg, Cd, Cr, Pb, etc. in many global populated areas were studied comprehensively, while our understanding towards thallium (Tl), an extremely toxic heavy metal, remains very limited. Further, the knowledge on atmospheric emissions, distribution, and the hidden risks associated with Tl is of great scarcity. Hence, this work aims to review recent data on significant sources of ambient Tl resulting from industrial activities, including Pb/Zn/Cu/Fe sulfide ore smelting, steel-making, coal burning, and cement production that involves the use of Tl-bearing wastes. Through the examination of Tl emissions and transfer pathways in the atmosphere, it is found that Tl is present at lower than ng/m3 in aerosols and air particulates but can increase to much higher levels even at 1000 µg/m3 in atmospheric fine particulate matters near the mining and smelting industrialized zones located near populated areas. This study highlights the importance of creating a comprehensive emission inventory for Tl, particularly in developing countries where this data is currently lacking. The time has come to develop a precise national emission inventory for Tl in order to prevent and mitigate the risks associated with ambient exposure to this element. This review offers novel insights for the scientific community and policy-makers in establishing effective control and management strategies to curb hidden Tl hazards derived from industrial activities.

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Novel psychoactive substances (NPS), such as Esketamine (Esket), often contaminate the aquatic ecosystems following human consumption, raising concerns about the residues and potential ecological hazards to non-target organisms. The study used zebrafish as a model organism to investigate the developmental toxicity and ecotoxicological effects of acute Esket exposure. Our findings demonstrate that exposure to Esket significantly affected the early development and angiogenesis of zebrafish embryos/larvae. The mandible length was significantly decreased, and the angles between the pharyngeal arch cartilages were narrowed compared to the control group (all P < 0.05). Additionally, Esket resulted in a decrease of 47.6-89.8 % in the number of neural crest cells (NCC). Transcriptome analysis indicated altered expression of genes associated with cartilage and osteoblast growth. Moreover, Esket significantly inhibited swimming ability in zebrafish larvae and was accompanied by behavioral abnormalities and molecular alterations in the brain. Potential mechanisms underlying Esket-induced behavioral disorders involve neurotransmitter system impairment, abnormal cartilage development and function, aberrant vascular development, as well as perturbations in oxidative stress and apoptosis signaling pathways. Notably, the dysregulation of skeleton development through the bone morphogenetic protein (BMP) signaling pathway is identified as the primary mechanistic behind Esket-induced behavioral disorder. This study enhances our understanding of Esket's ecotoxicology profile and provides a comprehensive assessment of the environmental risks associated with NPS.

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Schizophrenia (SZ) is a highly heritable mental disorder, and genome-wide association studies have identified the association between deleted in colorectal cancer (DCC) and SZ. Previous study has shown a lowered expression of DCC in the cerebral cortex of SZ patient. In this study, we identified novel single nucleotide polymorphisms (SNPs) of DCC statistically correlated with SZ. Based on these, we generated DCC conditional knockout (CKO) mice and explored behavioral phenotypes in these mice. We observed that deletion of DCC in cortical layer VI but not layer V led to deficits in fear and spatial memory, as well as defective sensorimotor gating revealed by the prepulse inhibition test (PPI). Critically, the defective sensorimotor gating could be restored by olanzapine, an antipsychotic drug. Furthermore, we found that the levels of p-AKT and p-GSK3α/ß were decreased, which was responsible for impaired PPI in the DCC-deficient mice. Finally, the DCC-deficient mice also displayed reduced spine density of pyramidal neurons and disturbed delta-oscillations. Our data, for the first time, identified and explored downstream substrates and signaling pathway of DCC which supports the hypothesis that DCC is a SZ-related risky gene and when defective, may promote SZ-like pathogenesis and behavioral phenotypes in mice.

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OBJECTIVE: Laparoendoscopic single-site myomectomy (LESS-M) is widely applied for the treatment of uterine leiomyoma. The purposes of this study were to investigate differences in hidden blood loss between LESS-M and conventional laparoscopic myomectomy (CLM) during treatment of uterine leiomyoma and to identify the associated risk factors. DESIGN: This is a retrospective study. PARTICIPANTS: The participants of this study were patients who underwent laparoscopic myomectomy (114 and 156 for LESS-M and CLM, respectively) between July 1, 2019, and October 10, 2020, at the Second Affiliated Hospital of Wenzhou Medical University. SETTING: The study was conducted at the Second Affiliated Hospital of Wenzhou Medical University. METHODS: We enrolled a total of 114 and 156 patients who were treated with LESS-M and CLM, respectively, between July 1, 2019, and October 10, 2020. We collected clinical data, then applied the Nadler and Gross formula and multiple linear regression analysis to calculate the HBL and identify the associated risk factors, respectively. RESULTS: Patients in the LESS-M group had a VBL of 115.4 ± 180.6 mL and an HBL of 364.3 ± 252.6 mL, accounting for 74.4 ± 22.4% of true TBL. On the other hand, patients in the CLM group had VBL of 187.9 ± 198.5 mL, and HBL of 306.8 ± 304.7 mL, accounting for 58.9 ± 30.2% of true TBL. HBL was significantly higher in the LESS-M than the CLM group (p = 0.000). LIMITATIONS: This study was the small sample size used. CONCLUSIONS: HBL accounted for a significant percentage of TBL in laparoscopic myomectomy, especially in patients treated with LESS-M. Paying attention to perioperative blood changes coupled with fully understanding HBL might promote postoperative recovery of patients.

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BACKGROUND: There has been a significant surge in animal studies of stem cell-derived extracellular vesicles (EVs) therapy for the treatment of premature ovarian failure (POF) but its efficacy remains unknown and a comprehensive and up-to-date meta-analysis is lacking. Before clinical translation, it is crucial to thoroughly understand the overall impact of stem cell-derived EVs on POF. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science were searched up to February 18, 2024. The risk of bias was evaluated according to Cochrane Handbook criteria, while quality of evidence was assessed using the SYRCLE system. The PRISMA guidance was followed. Trial sequential analysis was conducted to assess outcomes, and sensitivity analysis and publication bias analysis were performed using Stata 14. RESULTS: Data from 25 studies involving 339 animals were extracted and analyzed. The analysis revealed significant findings: stem cell-derived EVs increase ovary weight (SMD = 3.88; 95% CI: 2.50 ~ 5.25; P < 0.00001; I2 = 70%), pregnancy rate (RR = 3.88; 95% CI: 1.94 ~ 7.79; P = 0.0001; I2 = 0%), count of births (SMD = 2.17; 95% CI: 1.31 ~ 3.04; P < 0.00001; I2 = 69%) and counts of different types of follicles. In addition, it elevates the level of AMH (SMD = 4.15; 95% CI: 2.75 ~ 5.54; P < 0.00001; I2 = 88%) and E2 (SMD = 2.88; 95% CI: 2.02 ~ 3.73; P < 0.00001; I2 = 80%) expression, while reducing FSH expression (SMD = -5.05; 95% CI: -6.60 ~ -3.50; P < 0.00001; I2 = 90%). Subgroup analysis indicates that the source of EVs, animal species, modeling method, administration route, and test timepoint affected efficacy. Trial sequential analysis showed that there was sufficient evidence to confirm the effects of stem cell-derived EVs on birth counts, ovarian weights, and follicle counts. However, the impact of stem cell-derived EVs on pregnancy rates needs to be further demonstrated through more animal experimental evidence. CONCLUSIONS: Stem cell-derived EVs demonstrate safety and efficacy in treating POF animal models, with potential improvements in fertility outcomes. TRIAL REGISTRATION: PROSPERO registration number: CRD42024509699.

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Reactive nitrogen species (RNS) are more lethal than reactive oxygen species (ROS), which gives them a very promising future in the field of cancer treatment. However, there are still a few drugs available for RNS generation. In this work, two 5th-order nonlinear optical materials, FB-Fe(III)/SNP@PEG and FB-Fe(II)-FB/SNP@PEG, are synthesized. The outstanding nonlinear optical properties of FB-Fe(III)/SNP@PEG help to achieve generation of bounteous superoxide anions (O2•-) in deep tissues, while sodium nitroprusside (SNP) provides NO in the body, both of which are prerequisites for RNS generation. Meanwhile, type I and type II ROS were also generated under irradiation of a 1600 nm laser. Based on the synergistic effect of ROS and RNS, FB-Fe(III)/SNP@PEG induced mitochondrial damage and DNA fragmentation and inhibited tumor cells through apoptosis, possessing better therapeutic effects than FB-Fe(II)-FB/SNP@PEG. This work put forward an innovative strategy to achieve the cooperative release of RNS and ROS in deep tissues, which provides insights and ideas for applying nonlinear optical materials to RNS therapy.

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PURPOSE: To investigate whether personalized embryo transfer (pET) predicted by a modified RNA-sequencing-based endometrial receptivity test (rsERT) model can improve intrauterine pregnancy rate (IPR) in patients with a receptive window of implantation (WOI). DESIGN: A retrospective pilot study was conducted in the Center for Reproductive Medicine, Central South University, from January 2018 to December 2023. A total of 524 patients with receptive WOI results from rsERT were assigned into two groups based on whether they underwent conventional embryo transfer (conventional ET) or pET. Patients in the conventional ET were matched with those in the pET group at a 1:1 ratio using propensity score matching (PSM). RESULTS: Before PSM, the IPR (55.73% vs. 46.19%, P = 0.032) and implantation rate (IR) (47.51% vs. 34.03%, P = 0.000) in the pET group were significantly higher than that in the conventional ET group. However, the number and types of transferred embryos differed significantly between the two groups. After adjusting for confounding factors, IPR (57.38% vs. 44.81, P = 0.016) and IR (46.81% vs. 33.10%, P = 0.001) remained significantly higher in the pET group compared to the conventional ET group. The implantation failure rate was significantly lower in the pET group compared to controls (42.62% vs. 55.19%, P = 0.016). Additionally, the multiple-pregnancy rate was significantly higher in the pET group compared to the conventional ET group (10.29% vs. 1.68%, P = 0.001). CONCLUSIONS: Women with receptive WOI results could benefit from the receptivity-timed pET predicted by the newly refined rsERT. These findings provide a basis for future research in precision medicine for embryo transfer.

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Peanut (Arachis hypogaea L.) is a globally important oil and food crop frequently grown in arid, semi-arid, or dryland environments. Improving drought tolerance is a key goal for peanut crop improvement efforts. Here we present the genome assembly and gene model annotation for 'Line8', a peanut genotype bred from drought tolerant cultivars. Our assembly and annotation are the most contiguous and complete peanut genome resources currently available. The high contiguity of the Line8 assembly allowed us to explore structural variation both between peanut genotypes and subgenomes. We detect several large inversions between Line8 and other peanut genome assemblies, and there is a trend for the inversions between more genetically diverged genotypes to have higher gene content. We also relate patterns of subgenome exchange to structural variation between Line8 homeologous chromosomes. Unexpectedly, we discover that Line8 harbors an introgression from A.cardenasii, a diploid peanut relative and important donor of disease resistance alleles to peanut breeding populations. The fully resolved sequences of both haplotypes in this introgression provide the first in situ characterization of A.cardenasii candidate alleles that can be leveraged for future targeted improvement efforts. The completeness of our genome will support peanut biotechnology and broader research into the evolution of hybridization and polyploidy.

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BACKGROUND: Moderate to severe breast pain has major effects on the quality of life for patients. Patent Chinese medicines are widely used in the treatment of breast pain due to their stable dosage form and good efficacy. OBJECTIVE: To evaluate the beneficial effects and safety of Hongjin Xiaojie Capsule (HJXJC), a Chinese patent medicine, for the treatment of cyclical breast pain. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This is a multicenter, single-blind randomized controlled trial conducted in 3 medical centers in China from 2019 to 2021. Patients with moderate to severe cyclic breast pain were randomly divided into the intervention group (who took HJXJC, four capsules per dose, three times a day for 12 weeks) and the control group (waiting for the treatment) in a 1:1 ratio. MAIN OUTCOME MEASURES: The primary outcome was pain duration, and the patients recorded measurements at baseline and at the end of weeks 4, 8, 12 and 16 on a patient log card. RESULTS: The full analysis set (FAS) population included 298 participants (intervention group, n = 150; control group, n = 148), while the per-protocol analysis set (PPS) included 274 participants. After 12 weeks, the duration of breast pain was significantly shorter in the intervention group (FAS: mean difference, -6.69; 95% CI, -7.58 to -5.80; P < 0.01, vs control. PPS: mean difference, -7.09; 95% CI, -8.01 to -6.16; P < 0.01, vs control). The Short-form McGill Pain Questionnaire (SF-MPQ) scores were significantly lower in the intervention group (FAS: mean difference, -12.55; 95% CI, -13.90 to -11.21; P < 0.01, vs control. PPS: mean difference, -13.07; 95% CI, -14.48 to -11.66; P < 0.01, vs control). The above indicators continued to be significantly different through week 16. Moreover, in the intervention group, breast lumps shrank after 12 weeks and the size of breast lumps was statistically smaller than that in the control group (P < 0.05), whereas the sizes of breast nodules and uterine fibroid showed no statistically significant difference compared with the control group (P > 0.05). At weeks 8 and 12, the dysmenorrhea scores in the intervention group were lower than those in the control group (P < 0.05). No obvious adverse reactions were observed in any group. CONCLUSION: HJXJC can significantly shorten the duration of breast pain, reduce breast pain, reduce the size of breast lumps, and relieve dysmenorrhea. However, it has no significant effect on the size of breast nodules or uterine fibroid. TRIAL REGISTRATION: This trial has been registered at the ISRCTN Registry. Number: ISRCTN44184398. PLEASE CITE THIS ARTICLE AS: Zhang Q, Fan YY, Wu XQ, Huo YD, Wang CH, Liang SB, Wang T, Zhong R, Wang X, Lai BY, Pei XH, Liu JP. Hongjin Xiaojie Capsule, a Chinese patent medicine, for treating moderate to severe cyclical breast pain: A single-blind randomized controlled trial. J Integr Med. 2024; 22(5): 552-560.

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BACKGROUND: Commonly used cleaning brushes in the reprocessing of flexible endoscopes often cause damage within the working channels. AIM: To develop a spray flushing system to achieving effective cleaning of the working channels while minimizing damage. METHODS: This prospective study included 60 used endoscopes and 60 Teflon tubes randomly divided into a control group (n = 30) and an experimental group (n = 30). The material of Teflon tubes was the same as that of the endoscope working channel. Endoscopes in the control group were manually cleaned using traditional cleaning brushes, while those in the experimental group were cleaned using the newly developed spray flushing system. ATP levels, cleanliness, and microbiological testing of the working channels were measured. Additionally, Teflon tubes in the control group underwent 500 passes with a cleaning brush, while those in the experimental group were subjected to the spray flushing system, and channel damage was evaluated. RESULTS: The ATP levels (RLU) in the two groups were 32.5 (13-66) and 26 (16-40), respectively (P > 0.05). Cleanliness scores were 1.5 (1-2) and 1 (1-2), respectively (P > 0.05). Debris was found in 73.3% of the control group, which was significantly higher than 46.7% in the experimental group (P < 0.05). Microbiological tests for both groups yielded negative results. Teflon tube damage in the control group was rated at 4 (4-5.25), which was significantly higher than in the experimental group 4 (3-4) (P < 0.01). CONCLUSION: The spray flushing system demonstrated superior efficacy in removing debris and resulted in less damage to the endoscope working channels compared with traditional cleaning brushes.

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INTRODUCTION: The aim of the study was to investigate the association of parameters related to accommodation and convergence and axial elongation in basic intermittent exotropia (IXT) patients and the potential clinical predictors of axial length (AL) growth. METHODS: A total of 140 basic IXT patients were recruited in this study. The medians of AL growth in different age brackets were chosen to divide the subjects into group A (slower axial elongation group, n = 69) and group B (faster axial elongation group, n = 71). Parameters of dominant and nondominant eyes were compared and analyzed during the 12-month follow-up period. The parameters, including baseline refraction, angle of deviation, Newcastle control score (NCS), accommodative amplitude (AMP), accommodative facility (AMF), accommodative response, positive or negative relative accommodation (PRA/NRA), and near point of convergence (NPC), were analyzed via univariate and multivariate regression. RESULTS: Subjects in the faster axial elongation group tended to have more myopic spherical equivalents (t = 3.956, p < 0.001), greater AMPs of dominant eyes (t = -2.238, p = 0.027), and fewer near points of convergence (t = 2.347, p = 0.020) than in the slower axial elongation group. For dominant eyes, logistic and linear regression analysis revealed that more negative spherical equivalents (OR = 0.603, p < 0.001; ß = -0.045, p < 0.001), greater AMPs (OR = 1.201, p = 0.027; ß = 0.023, p = 0.010), and less near points of convergence (OR = 0.883, p = 0.021; ß = -0.012, p = 0.019) were correlated with the faster axial elongation. For nondominant eyes, a more myopic spherical equivalent (OR = 0.682; p = 0.001; ß = -0.029, p = 0.005) was the only parameter correlated with faster axial elongation through regression analysis. CONCLUSION: In children with basic IXT, faster axial elongation in the dominant eyes was associated with more myopic spherical equivalents, greater AMPs, and lower NPCs. These accommodative parameters can serve as potential clinical indicators for monitoring myopia progression in addition to AL.

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The brominated flame retardant 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) widely used in manufacturing is inevitably released into the environment, resulting in the exposure of organisms to BTBPE. Therefore, it is particularly important to explore its toxic mechanism. The liver is one of the main accumulating organs of BTBPE, but the mechanism underlying BTBPE hepatotoxicity has not been thoroughly investigated. In our study, BTBPE was administered to Sprague-Dawley (SD) rats and rat hepatocytes (BRL cells) in vivo and in vitro, respectively, and HE staining, AO/EB staining, fluorescent probes, qPCR, immunofluorescence, and dual-luciferase reporter assays were performed. We investigated the mechanism of action of growth arrest-specific 5 (GAS5), miR-743a-5p, and NUAK family kinase 1 (NUAK1) in BTBPE-induced necroptosis from the perspective of competing endogenous RNAs (ceRNAs) using NUAK1 inhibitors, siRNAs, mimics, and overexpression plasmids. Our study showed that exposure to BTBPE caused necroptosis in the liver and BRL cells, accompanied by an oxidation-reduction imbalance and an inflammatory response. It is worth noting that NUAK1 is a newly discovered upstream regulatory target for necroptosis. In addition, miR-743a-5p was shown to inhibit necroptosis by targeting NUAK1 and down-regulating NUAK1. GAS5 upregulates NUAK1 expression by competitively binding to miR-743a-5p, thereby inducing necroptosis. This study demonstrated, for the first time, that the GAS5-miR-743a-5p-NUAK1 axis is involved in the regulation of necroptosis via ceRNAs. Thus, GAS5 and NUAK1 induce necroptosis by competitively binding to miR-743a-5p.

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