Degradation of the novel herbicide tiafenacil in aqueous solution: Kinetics, various influencing factors, hydrolysis products identification, and toxicity assessment.

As new pesticides are continually introduced into agricultural systems, understanding their environmental behavior and potential toxicity effects is crucial for effective risk assessment. This study utilized QuEChERS and UPLC-QTOF-MS/MS techniques to analyze Tiafenacil (TFA) and its six hydrolysis products (HP1 to HP6) in water, marking the first comprehensive report on these degradation products. Calibration curves demonstrated strong linearity (R2 ≥ 0.9903) across concentrations ranging from 0.02 to 3.50 mg L-1. TFA's hydrolysis followed single first-order kinetic (SFOK) model, with rapid degradation observed under alkaline and high-temperature conditions, resulting in half-lives ranging from 0.22 to 84.82 days. The ECOSAR model predicts that TFA's hydrolysis products exhibit acute and chronic toxicity to fish, Daphnia, and green algae. Additionally, hydrolysis products HP1, HP5, and HP6 were detected in irrigation water from citrus orchards, posing higher predicted toxicity risks to fish and green algae. This highlights the necessity for further risk assessments considering transformation products. Overall, this study enhances our understanding of TFA's environmental fate and supports its safe agricultural application and monitoring practices.

Association of Female Reproductive Factors with depression and suicidal ideation in postmenopausal women: Evidence from NHANES 2007-2018.

OBJECTIVE: This cross-sectional research aimed to examine how reproductive factors influence depression and suicidal ideation among postmenopausal women. METHODS: Data from the 2007 to 2018 US National Health and Nutrition Examination Survey were analyzed for this study. The Patient Health Questionnaire (PHQ-9) was adopted to measure depression and suicidal ideation in the participants. RESULTS: Out of 3076 participants, 9.5% (348/3076) experienced depression, and 3.4% (128/3076) reported suicidal ideation. Following the adjustment for confounding factors, premature menopause (OR = 1.81, 95% CI: 1.03-3.15) was significantly associated with an increased risk of depression. Moreover, postmenopausal women with a higher number of pregnancies exhibited a greater risk of depression (OR = 1.29, 95% CI: 1.09-1.53; P < 0.001). Conversely, a longer reproductive lifespan (OR = 0.96, 95% CI: 0.93-0.99) and a higher number of livebirths (OR = 0.68, 95% CI: 0.54-0.86; P < 0.001) were linked to a decreased risk of depression. Furthermore, the use of oral contraceptives (OR = 0.52, 95% CI: 0.28-0.97; P = 0.021) was significantly associated with a decreased likelihood of experiencing suicidal ideation, while the number of livebirths (OR = 0.68, 95% CI: 0.48-0.97; P = 0.018) exhibited a negative correlation with suicidal ideation. CONCLUSION: Our results indicate that reproductive factors are significantly associated with the risk of depression and suicidal ideation in postmenopausal women. Further longitudinal studies with repeated measures of depression are necessary to establish causal relationships.

Concurrent Analysis of Tiafenacil and Its Transformation Products in Soil by Using Newly Developed UHPLC-QTOF-MS/MS-Based Approaches.

As new pesticides continue to emerge in agricultural systems, understanding their environmental behavior is crucial for effective risk assessment. Tiafenacil (TFA), a promising novel pyrimidinedione herbicide, was the focus of this study. We developed an efficient QuEChERS-UHPLC-QTOF-MS/MS method to measure TFA and its transformation products (TP1, TP2, TP3, TP4, and TP5) in soil. Our calibration curves exhibited strong linearity (R2 ≥ 0.9949) ranging from 0.015 to 2.0 mg/kg within a low limit of quantification (LOQ) of 2.0 µg/kg. Inter-day and intra-day recoveries (0.10 to 2.0 mg/kg, 80.59% to 110.05%, RSD from 0.28% to 12.93%) demonstrated high sensitivity and accuracy. Additionally, TFA dissipation under aerobic conditions followed first-order kinetics, mainly yielding TP1 and TP4. In contrast, TP1 and TP2 were mainly found under sterilized and anaerobic conditions, and TFA dissipation followed second-order kinetics. Moreover, we predicted the transformation pathways of TFA using density functional theory (DFT) and assessed the toxicity levels of TFA and its TPs to aquatic organisms using ECOSAR. Collectively, these findings hold significant implications for a better understanding of TFA fate in diversified soil, benefiting its risk assessment and rational utilization.

Alteration of bone microarchitecture in hereditary distal RTA patients with SLC4A1 gene mutation: assessed by HR-pQCT.

CONTEXT: Hereditary distal renal tubular acidosis caused by SLC4A1 gene mutation (SLC4A1-dRTA) is a rare hereditary form of renal tubular acidosis. Rickets or osteomalacia is a common complication of SLC4A1-dRTA, and seriously affects patients' daily life. However, studies on the bone microstructure in SLC4A1-dRTA are limited. OBJECTIVE: This work aimed to evaluate the bone microstructure of SLC4A1-dRTA patients, compared to age- and sex-matched healthy controls and X-linked hypophosphatemic rickets (XLH) patients. METHODS: This was a retrospective study on eleven SLC4A1-dRTA patients. Clinical manifestations, biochemical and radiographical examinations were characterized. Bone microstructure was examined in seven SLC4A1-dRTA patients, seven healthy controls and twenty-one XLH patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: Skeletal symptoms, including fracture, bone pain, and lower limb deformity, were presented in 72.7% of SLC4A1-dRTA patients. Short stature was presented in 63.6% of the patients. SLC4A1-dRTA patients had significantly lower volumetric BMD in the distal tibia, and more severe deteriorated trabecular bone in the distal radius and tibia than healthy controls. SLC4A1-dRTA patients had significantly more severe deteriorated trabecular bone in the distal radius and distal tibia compared to XLH patients. With long-term alkaline therapy, SLC4A1-dRTA patients had alleviation in bone pain, increase in height. CONCLUSIONS: Skeletal lesions were common clinical manifestations in SLC4A1-dRTA patients. Compared with XLH, another common type of rickets, SLC4A1-dRTA patients had more severe trabecular bone microstructure damage, further supporting the necessity of early diagnosis and timely treatment of the disease.

SPI1-mediated macrophage polarization aggravates age-related macular degeneration.

Objective: This study revealed a core regulator and common upstream mechanisms for the multifaceted pathological processes of age-related macular degeneration (AMD) and provided proof-of-concept for this new therapeutic target. Methods: Comprehensive gene expression analysis was performed using RNA sequencing of eye cup from old mice as well as laser-induced choroidal neovascularization (CNV) mouse model. Through integrative analysis and protein-protein interaction (PPI) analysis, common pathways and key transcription factor was identified simultaneously engaged in age-related retinal degeneration and CNV, the two typical pathological process of AMD. Subsequently, the expression changes of Spi1, the key regulator, as well as the alternation of the downstream mechanisms were validated in both models through qRT-PCR, Elisa, flow cytometry and immunofluorescence. Further, we assessed the impact of Spi1 knockdown in vitro and in vivo using gene intervention vectors carried by adeno-associated virus or lentivirus to test its potential as a therapeutic target. Results: Compared to corresponding controls, we found 1,939 and 1,319 genes differentially expressed in eye cups of old and CNV mice respectively. The integrative analysis identified a total of 275 overlapping DEGs, of which 150 genes were co-upregulated. PPI analysis verified a central transcription factor, SPI1. The significant upregulation of Spi1 expression was then validated in both models, accompanied by macrophage polarization towards the M1 phenotype. Finally, SPI1 suppression significantly inhibited M1 polarization of BMDMs and attenuated neovascularization in CNV mice. Conclusion: This study demonstrates that SPI1 exerts a pivotal role in AMD by regulation of macrophage polarization and innate immune response, offering promise as an innovative target for treating AMD.

An unenhanced 3D-FLAIR sequence using long repetition time and constant flip angle to image endolymphatic hydrops.

OBJECTIVES: To evaluate a three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence using a long repetition time (TR) and constant flip angle (CFA) in differentiating between perilymph and endolymph in a phantom study, and unenhanced endolymphatic hydrops (EH) imaging in a patient study. METHODS: Three solutions in similar ion and protein concentrations with endolymph, perilymph, and cerebrospinal fluid were prepared for variable flip angle (VFA) 3D-FLAIR (TR 10,000 ms) and CFA (120°) 3D-FLAIR using different TR (10,000, 16,000, and 20,000 ms). Fifty-two patients with probable or definite Meniere's disease received unenhanced CFA (120°) 3D-FLAIR using a long TR (20,000 ms) and 4-h-delay enhanced CFA (120°) 3D-FLAIR (TR 16,000 ms). Image quality, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of them were compared. Agreement in the evaluation of the EH degree between them was analyzed. RESULTS: In the phantom study, CNRs between perilymphatic and endolymphatic samples of VFA 3D-FLAIR (TR 10,000 ms) and CFA 3D-FLAIR (TR 10,000, 16,000, and 20,000 ms) were 6.66 ± 1.30, 17.90 ± 2.76, 23.87 ± 3.09, and 28.22 ± 3.15 (p < 0.001). In patient study, average score (3.65 ± 0.48 vs. 4.19 ± 0.40), SNR (34.56 ± 9.80 vs. 51.40 ± 11.27), and CNR (30.66 ± 10.55 vs. 45.08 ± 12.27) of unenhanced 3D-FLAIR were lower than enhanced 3D-FLAIR (p < 0.001). Evaluations of the two sequences showed excellent agreement in the cochlear and vestibule (Kappa value: 0.898 and 0.909). CONCLUSIONS: The CFA 3D-FLAIR sequence using a long TR could be used in unenhanced EH imaging with high accuracy. CLINICAL RELEVANCE STATEMENT: Unenhanced imaging of endolymphatic hydrops is valuable in the diagnosis and follow-up of patients, especially those who cannot receive contrast-enhanced MRI. KEY POINTS: Ion and protein concentration differences can be utilized in differentiating endolymph and perilymph on MRI. Endolymphatic and perilymphatic samples could be differentiated in vitro on this 3D-FLAIR sequence. This unenhanced 3D-FLAIR sequence is in excellent agreement with the enhanced constant flip angle 3D-FLAIR sequence.

Physical literacy and health of Chinese medical students: the chain mediating role of physical activity and subjective well-being.

Background/objective: While Physical Literacy has been highlighted as a determinant in health in recent study, there is a dearth of studies examining its effect on physical health, and there is a little in the way of empirical data linking Physical Literacy to health outcomes. Accordingly, further empirical research is needed to clarify the mechanisms by which Physical Literacy affects physical health. The purpose of this study was to verify the role of medical students' Physical Literacy on Health-related quality of life as well as to explore the chain mediating role of Physical Activity and Subjective Well-being in it. Methods: This study utilized a cross-sectional study design. The Physical Literacy, Health-related Quality of Life, Physical Activity ratings, and Subjective Well-being of students at Shanxi Medical University were all measured using an online survey administered in September 2023. A total of 1968 valid questionnaires were returned. First, descriptive statistics and correlation analysis were performed using SPSS software. Second, PROCESS was used to test the mediating role. Finally, we used structural equation modeling (Amos) to test the model fit. Results: There is a significant correlation between all variables. After mediation effects analysis, we found that there were three indirect pathways of physical literacy on health-related quality of life: a single mediating effect of physical activity, a single mediating effect of subjective well-being, and a chained mediating effect of physical activity-subjective well-being. Conclusion: The mediating role of physical activity and subjective well-being on the relationship between physical literacy and health-related quality of life has been confirmed. Our research results support the integration of physical literacy into physical education teaching and the modification of curriculum content by physical education teachers as part of efforts to enhance students' physical activity levels, subjective well-being levels, and overall health. This study provides a new perspective for intervention in improving the health of medical students.

Comparative time-dependent proteomics reveal the tolerance of cancer cells to magnetic iron oxide nanoparticles.

Cancer is one of the most challenging diseases in the world. Recently, iron oxide nanoparticles (IONPs) are emerging materials with rapid development and high application value, and have shown great potential on tumor therapy due to their unique magnetic and biocompatible properties. However, some data hint us that IONPs were toxic to normal cells and vital organs. Thus, more data on biosafety evaluation is urgently needed. In this study, we compared the effects of silicon-coated IONPs (Si-IONPs) on two cell types: the tumor cells (Hela) and the normal cells (HEK293T, as 293 T for short), compared differences of protein composition, allocation and physical characteristics between these two cells. The major findings of our study pointed out that 293 T cells death occurred more significant than that of Hela cells after Si-IONPs treatment, and the rate and content of endocytosis of Si-IONPs in 293 T cells was more prominent than in Hela cells. Our results also showed Si-IONPs significant promoted the production of reactive oxygen species and disturbed pathways related to oxidative stress, iron homeostasis, apoptosis and ferroptosis in both two types of cells, however, Hela cells recovered from these disturbances more easily than 293 T. In conclusion, compared with Hela cells, IONPs are more likely to induce 293 T cells death and Hela cells have their own unique mechanisms to defense invaders, reminding scientists that future in vivo and in vitro studies of nanoparticles need to be cautious, and more safety data are needed for further clinical treatment.

Quantification of MicroRNA in a Single Living Cell via Ionic Current Rectification-Based Nanopore for Triple Negative Breast Cancer Diagnosis.

Accurate analysis of microRNAs (miRNAs) at the single-cell level is extremely important for deeply understanding their multiple and intricate biological functions. Despite some advancements in analyzing single-cell miRNAs, challenges such as intracellular interferences and insufficient detection limits still remain. In this work, an ultrasensitive nanopore sensor for quantitative single-cell miRNA-155 detection is constructed based on ionic current rectification (ICR) coupled with enzyme-free catalytic hairpin assembly (CHA). Benefiting from the enzyme-free CHA amplification strategy, the detection limit of the nanopore sensor for miRNA-155 reaches 10 fM and the nanopore sensor is more adaptable to complex intracellular environments. With the nanopore sensor, the concentration of miRNA-155 in living single cells is quantified to realize the early diagnosis of triple-negative breast cancer (TNBC). Furthermore, the nanopore sensor can be applied in screening anticancer drugs by tracking the expression level of miRNA-155. This work provides an adaptive and universal method for quantitatively analyzing intracellular miRNAs, which will greatly improve our understanding of cell heterogeneity and provide a more reliable scientific basis for exploring major diseases at the single-cell level.

A nonsense CC2D1A variant is associated with congenital anomalies, motor delay, hypotonia, and slight deformities.

Background: Autosomal recessive intellectual developmental disorder-3 is caused by homozygous or compound heterozygous mutations in the CC2D1A gene. The disorder is characterized by intellectual disability (ID) and autism spectrum disorder (ASD). To date, 39 patients from 17 families with CC2D1A -related disorders have been reported worldwide, in whom only six pathogenic or likely pathogenic loss-of-function variants and three variants of uncertain significance (VUS) in the CC2D1A gene have been identified in these patients. Methods: We described a patient with ID from a non-consanguineous Chinese family and whole-exome sequencing (WES) was used to identify the causative gene. Results: The patient presented with severe ID and ASD, speech impairment, motor delay, hypotonia, slight facial anomalies, and finger deformities. Threatened abortion and abnormal fetal movements occurred during pregnancy with the proband but not his older healthy sister. WES analysis identified a homozygous nonsense variant, c.736C > T (p.Gln246Ter), in the CC2D1A gene. In addition, six novel likely pathogenic CC2D1A variants were identified by a retrospective review of the in-house database. Conclusions: This study expands the genetic and clinical spectra of CC2D1A-associated disorders, and may aid in increasing awareness of this rare condition. Our findings have provided new insights into the clinical heterogeneity of the disease and further phenotype-genotype correlation, which could help to offer scope for more accurate genetic testing and counseling to affected families.

Local knowledge of homegarden plants in Miao ethnic communities in Laershan region, Xiangxi area, China.

BACKGROUND: Homegardens are small-scale land use systems with significant implications for local livelihoods, biodiversity conservation, and sustainable development due to their diverse flora and fauna. Conducting homegarden surveys enables researchers to gain insights into the traditional ecological knowledge of indigenous communities, preserve homegarden biodiversity, and promote sustainable livelihoods. This study has two objectives: first, to collect, record, and organize data on homegarden plants and related traditional knowledge from three communities in the Laershan Plateau, and second, to analyze the species and functional diversity of homegarden plants in the region while exploring the factors that contribute to the heterogeneous distribution of these plants among the communities of three townships. METHODS: This research employed field surveys in the Laershan Miao Autonomous Region in Xiangxi, China, from September 2021 to August 2023. Data were collected through observation and semi-structured interviews. The study utilized descriptive statistics and quantitative analysis, including the Relative Importance Value (RI), Use Value Index (UV), Jaccard Index (JI), and Comprehensive Index of Land Use Degree (La), to examine the diversity of local homegarden plants and related traditional knowledge, as well as community heterogeneity. RESULTS: The study area exhibited rich biodiversity, with 152 plant species recorded belonging to 62 families and 124 genera. These findings highlight the importance of homegarden plants in maintaining ecological balance and enhancing system resilience against disturbances. Homegarden plants serve multiple functions such as food, ornamental, medicinal, and fodder purposes, with edible and trade plants having the most abundant knowledge. Furthermore, this research revealed that communities with similar forest resource compositions may have similar homegarden plant compositions, demonstrating the connection between cultural exchange among different communities and patterns of plant species distribution. CONCLUSIONS: The Laershan region boasts diverse homegarden plant species crucial for ecological balance and resilience. Their multifunctionality reflects human impact. Plant diversity varies with residents' lifestyles, needs, and cultural exchanges. The close connection between plants and local life is clear. Factors like resource distribution, cultural exchange, and lifestyle influence plant distribution. Further research is needed for conservation and sustainable development. Future research should focus on culturally valuable plant species and traditional knowledge applications.

Clinical and genetic analysis of trichohepatoneurodevelopmental syndrome caused by a CCDC47 variant.

Trichohepatoneurodevelopmental syndrome is an extremely uncommon autosomal recessive disorder resulting from variants in the CCDC47 gene, which encodes a Ca2+-binding endoplasmic reticulum (ER) transmembrane protein. To date, only four patients with CCDC47 deficiency have been reported, all of them with homozygous truncating CCDC47 variants. For this study, a Chinese family was recruited, which included a patient diagnosed with trichohepatoneurodevelopmental syndrome. Whole exome sequencing (WES) identified the proband's novel homozygous CCDC47 variation (NM_020198: c.634C > T(p.Arg212*). The variant was confirmed to be segregating in the proband and her unaffected relatives through Sanger sequencing. The patient described exhibited a clinical phenotype similar to that of patients with the CCDC47 variant. Compared to reported cases with CCDC47 pathogenic variants, our patients showed a novel complication of hearing impairment. In addition, brain abnormalities, small feet, bilateral hip dislocation, hip dysplasia, overlapping toes, pectus excavatum, scoliosis and narrow chest were not observed in our patient. We also examined five different variations and their corresponding phenotypes from five patients, both in current and previous research. Although some clinical manifestations of trichohepatoneurodevelopmental syndrome were highly variable, the most common phenotypes observed in these patients include microcephaly, profound intellectual disability, severe global development delay, pronounced growth restriction, hypotonia, woolly hair, facial dysmorphism, respiratory and visual abnormalities, gastrointestinal abnormalities, liver dysfunction, pruritus, skeletal and limb abnormalities, congenital heart defects and immunodeficiency. The present report is the first of a Chinese infant with homozygous variant in the CCDC47 gene. We expanded the genetic and phenotypic spectrum associated with trichohepatoneurodevelopmental syndrome.

Novel germline variants in KMT2C in Chinese patients with Kleefstra syndrome-2.

Kleefstra syndrome (KLEFS) refers to a rare inherited neurodevelopmental disorder characterized by intellectual disability (ID), language and motor delays, behavioral abnormalities, abnormal facial appearance, and other variable clinical features. KLEFS is subdivided into two subtypes: Kleefstra syndrome-1 (KLEFS1, OMIM: 610253), caused by a heterozygous microdeletion encompassing the Euchromatic Histone Lysine Methyltransferase 1 (EHMT1) gene on chromosome 9q34.3 or pathogenic variants in the EHMT1 gene, and Kleefstra syndrome-2 (KLEFS2, OMIM: 617768), caused by pathogenic variants in the KMT2C gene. More than 100 cases of KLEFS1 have been reported with pathogenic variants in the EHMT1 gene. However, only 13 patients with KLEFS2 have been reported to date. In the present study, five unrelated Chinese patients were diagnosed with KLEFS2 caused by KMT2C variants through whole-exome sequencing (WES). We identified five different variants of the KMT2C gene in these patients: c.9166C>T (p.Gln3056*), c.9232_9247delCAGCGATCAGAACCGT (p.Gln3078fs*13), c.5068dupA (p.Arg1690fs*10), c.10815_10819delAAGAA (p.Lys3605fs*7), and c.6911_6912insA (p.Met2304fs*8). All five patients had a clinical profile similar to that of patients with KLEFS2. To analyze the correlation between the genotype and phenotype of KLEFS2, we examined 18 variants and their associated phenotypes in 18 patients with KLEFS2. Patients carrying KMT2C variants presented with a wide range of phenotypic defects and an extremely variable phenotype. We concluded that the core phenotypes associated with KMT2C variants were intellectual disability, facial dysmorphisms, language and motor delays, behavioral abnormalities, hypotonia, short stature, and weight loss. Additionally, sex may be one factor influencing the outcome. Our findings expand the phenotypic and genetic spectrum of KLEFS2 and help to clarify the genotype-phenotype correlation.

Insights into the time-course cellular effects triggered by iron oxide nanoparticles by combining proteomics with the traditional pharmacology strategy.

In recent years, a number of initially approved magnetic iron oxide nanoparticle (IONP)-based nano-medicines have been withdrawn due to the obscure nano-bio effects. Therefore, there is an urgent need to study the cellular effects triggered by IONPs on cells. In this study, we investigate the time-course cellular effects on the response of RAW 264.7 cells caused by Si-IONPs via pharmacological and mass spectrometry-based proteomics techniques. Our results revealed that Si-IONPs were internalized by clathrin-mediated endocytosis within 1 hour, and gradually degraded in endolysosomes over time, which might influence autophagy, oxidative stress, innate immune response, and inflammatory response after 12 hours. Our research provides a necessary assessment of Si-IONPs for further clinical treatment.

Advances in Monte Carlo Method for Simulating the Electrical Percolation Behavior of Conductive Polymer Composites with a Carbon-Based Filling.

Conductive polymer composites (CPCs) filled with carbon-based materials are widely used in the fields of antistatic, electromagnetic interference shielding, and wearable electronic devices. The conductivity of CPCs with a carbon-based filling is reflected by their electrical percolation behavior and is the focus of research in this field. Compared to experimental methods, Monte Carlo simulations can predict the conductivity and analyze the factors affecting the conductivity from a microscopic perspective, which greatly reduces the number of experiments and provides a basis for structural design of conductive polymers. This review focuses on Monte Carlo models of CPCs with a carbon-based filling. First, the theoretical basis of the model's construction is introduced, and a Monte Carlo simulation of the electrical percolation behaviors of spherical-, rod-, disk-, and hybridfilled polymers and the analysis of the factors influencing the electrical percolation behavior from a microscopic point of view are summarized. In addition, the paper summarizes the progress of polymer piezoresistive models and polymer foaming structure models that are more relevant to practical applications; finally, we discuss the shortcomings and future research trends of existing Monte Carlo models of CPCs with carbon-based fillings.

Transfer RNA derived fragment, tRF-Glu-CTC, aggravates the development of neovascular age-related macular degeneration.

Rationale: Angiogenesis expedites tissue impairment in many diseases, including age-related macular degeneration (AMD), a leading cause of irreversible blindness in elderly. A substantial proportion of neovascular AMD patients, characterized by aberrant choroidal neovascularization (CNV), exhibit poor responses or adverse reactions to anti-VEGF therapy. Herein, we aimed to unveil the function of newly identified transfer RNA-derived small RNA, tRF-Glu-CTC, in the pathology of CNV and determine its potential in inhibiting angiogenesis. Methods: Small non-coding RNA sequencing and quantitative polymerase chain reaction were conducted to detect expression pattern of tRF-Glu-CTC in CNV development. Immunofluorescence staining, fundus fluorescein angiography and ex vivo choroidal sprouting assays were employed for the evaluation of tRF-Glu-CTC's function in CNV development. The role of tRF-Glu-CTC in endothelial cells were determined by in vitro endothelial cell proliferation, migration and tube formation assays. Transcriptome sequencing, dual-luciferase reporter assay and in vitro experiments were conducted to investigate downstream mechanism of tRF-Glu-CTC mediated pathology. Results: tRF-Glu-CTC exhibited substantial up-regulation in AMD patients, laser-induced CNV model, and endothelial cells under hypoxia condition, which is a hallmark of CNV. Inhibiting tRF-Glu-CTC reduced angiogenesis and hypoxia stress in the neovascular region without neuroretina toxicity in laser-induced CNV model, showing an anti-angiogenic effect comparable to bevacizumab, while overexpression of tRF-Glu-CTC significantly augmented CNV. Mechanically, under hypoxia condition, angiogenin was involved in the production of tRF-Glu-CTC, which in turn triggered endothelial cell tubulogenesis, migration and promoted the secretion of inflammatory factors via the suppression of vasohibin 1 (VASH1). When downregulating VASH1 expression, the inhibition of tRF-Glu-CTC showed minimal suppression on angiogenesis. Conclusions: This study demonstrated the important role of tRF-Glu-CTC in the progression of angiogenesis. Targeting of tRF-Glu-CTC may be an alternative to current anti-VEGF therapy for CNV in AMD and other conditions with angiogenesis.

Novel variants in TNRC6B cause global developmental delay with speech and behavioral abnormalities, short stature, low body weight, café-au-lait spots, and metabolic abnormality.

BACKGROUND: TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease mainly characterized by facial dysmorphism, developmental delay/intellectual disability (DD/ID), speech and language delay, fine and motor delay, attention deficit and hyperactivity disorder (ADHD), and variable behavioral abnormalities. It is caused by heterozygous variant in the TNRC6B gene (NM_001162501.2, MIM 610740), which encodes the trinucleotide repeat-containing adaptor 6B protein. METHODS: In this study, two Chinese patients with TNRC6B deficiency syndrome were recruited, and genomic DNA extraction from peripheral blood leukocytes of these parents and their family members was extracted for whole-exome sequencing and Sanger sequencing. RESULTS: Here, we report two unrelated Chinese patients diagnosed with TNRC6B deficiency syndrome caused by novel de novo likely pathogenic or pathogenic TNRC6B variants c.335C>T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63), which expands the genetic spectrum of TNRC6B deficiency syndrome. The clinical features of the patients were DD/ID, delayed speech, ADHD, behavioral abnormalities, short stature, low body weight, café-au-lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures, which expands the phenotype spectrum associated with TNRC6B deficiency syndrome. CONCLUSION: This study expands the genotypic and phenotypic spectrum of TNRC6B deficiency syndrome. Our findings indicate that patients with TNRC6B deficiency syndrome should be monitored for growth and metabolic problems and therapeutic strategies should be developed to address these problems. Our report also suggests the clinical diversity of TNRC6B deficiency syndrome.

Celastrol induces premature ovarian insufficiency by inducing apoptosis in granulosa cells.

Celastrol, a natural compound purified from the Chinese herb Tripterygium wilfordii Hook. f., has excellent pharmacological activity for the treatment of various diseases. Assessing the safety of its use is essential for its development into a clinical medicine. However, research assessing its toxicity on the female reproductive system has never been reported. In this study, the ovarian toxicity of celastrol and its underlying mechanism were investigated. We found that celastrol induced premature ovarian insufficiency and apoptosis in granulosa cells. Activity-based protein profiling results showed that high mobility group box 1 was a candidate target protein of celastrol. Celastrol directly bound to Cys106 of high mobility group box 1. Knocking down high mobility group box 1 induced apoptosis of granulosa cells, while overexpression of this gene reversed celastrol-induced apoptosis. Celastrol treatment upregulated p21 transcription, but overexpression of high mobility group box 1 reversed this upregulation. Thus, Celastrol induces premature ovarian insufficiency and apoptosis in granulosa cells by directly binding to high mobility group box 1 and interfering with its biological function to regulate p21 transcription. This study provides valuable information for assessing the safety of the clinical application of celastrol on female patients.

Threefold coordinated germanium in a GeO2 melt.

The local structure around germanium is a fundamental issue in material science and geochemistry. In the prevailing viewpoint, germanium in GeO2 melt is coordinated by at least four oxygen atoms. However, the viewpoint has been debated for decades due to several unexplained bands present in the GeO2 melt Raman spectra. Using in situ Raman spectroscopy and density functional theory (DFT) computation, we have found a [GeOØ2]n (Ø = bridging oxygen) chain structure in a GeO2 melt. In this structure, the germanium atom is coordinated by three oxygen atoms and interacts weakly with two neighbouring non-bridging oxygen atoms. The bonding nature of the chain has been analyzed on the basis of the computational electronic structure. The results may settle down the longstanding debate on the GeO2 melt structure and modify our view on germanate chemistry.

Circulating miR-320b Contributes to CD4+ T-Cell Proliferation in Systemic Lupus Erythematosus via MAP3K1.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies and tissue inflammation. Mesenchymal stem cells (MSCs) have emerged as a promising candidate therapy for SLE owing to the immunomodulatory and regenerative properties. Circulating miRNAs are small, single-stranded noncoding RNAs in a variety of body fluids that regulate numerous immunologic and inflammatory pathways. Recent studies have revealed many differentially expressed circulating miRNAs in autoimmune diseases including SLE. However, the role of circulating miRNAs in SLE has not been extensively studied. Here, we performed small RNA sequencing analysis to compare the circulating miRNA profiles of SLE patients before and after MSC transplantation (MSCT), and identified a significant decrease of circulating miR-320b level during MSCT. Importantly, we found that the expression of circulating miR-320b and its target gene MAP3K1 was closely associated with SLE disease activity. The in vitro experiments showed that decreased MAP3K1 level in SLE peripheral blood mononuclear cells (PBMCs) was involved in CD4+ T-cell proliferation. In MRL/lpr mice, miR-320b overexpression aggravated symptoms of SLE, while miR-320b inhibition could promote disease remission. Besides, MSCs regulate miR-320b/MAP3K1 expression both in vitro and in vivo. Our results suggested that circulating miR-320b and MAP3K1 may be involved in CD4+ T-cell proliferation in SLE. This trial is registered with NCT01741857.