Targeting hTERT Promoter G-Quadruplex DNA Structures with Small-Molecule Ligand to Downregulate hTERT Expression for Triple-Negative Breast Cancer Therapy.

Human telomerase reverse transcriptase (hTERT) may have noncanonical functions in transcriptional regulation and metabolic reprogramming in cancer cells, but it is a challenging target. We thus developed small-molecule ligands targeting hTERT promoter G-quadruplex DNA structures (hTERT G4) to downregulate hTERT expression. Ligand 5 showed high affinity toward hTERT G4 (Kd = 1.1 µM) and potent activity against triple-negative breast cancer cells (MDA-MB-231, IC50 = 1 µM). In cell-based assays, 5 not only exerts markedly inhibitory activity on classical telomere functions including decreased telomerase activity, shortened telomere length, and cellular senescence but also induces DNA damage, acute cellular senescence, and apoptosis. This study reveals that hTERT G4-targeting ligand may cause mitochondrial dysfunction, disrupt iron metabolism and activate ferroptosis in cancer cells. The in vivo antitumor efficacy of 5 was also evaluated in an MDA-MB-231 xenograft mouse model and approximately 78.7% tumor weight reduction was achieved. No observable toxicity against the major organs was observed.

Safety and efficacy of PCSK9 inhibitor (evolocumab) in patients with non-ST segment elevation acute coronary syndrome and non-culprit artery critical lesions: a randomised controlled trial protocol (SPECIAL study).

INTRODUCTION: Patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) and concomitant multivessel coronary artery disease (CAD) are considered patients with extremely high-risk atherosclerotic cardiovascular disease (ASCVD), and current guidelines specify a lower low-density lipoprotein cholesterol (LDL-C) target for this population. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to effectively reduce LDL-C levels on a statin background. Additionally, several studies have confirmed the role of PCSK9 inhibitors in plaque regression and reducing residual cardiovascular risk in patients with ACS. However, those studies included coronary lesions with a degree of stenosis <50%. Whether the application of PCSK9 inhibitors in patients with NSTE-ACS with non-culprit artery critical lesions (stenosis degree between 50% and 75%) has a similar effect on plaque regression and improvement of cardiovascular outcomes remains unknown, with a lack of relevant research. This study aims to further investigate the safety and efficacy of evolocumab in patients with NSTE-ACS and concomitant multivessel CAD (non-culprit artery stenosis between 50% and 75%). METHODS AND ANALYSIS: In this single-centre clinical randomised controlled trial, 122 patients with NSTE-ACS and concomitant multivessel CAD (non-culprit artery stenosis between 50% and 75%) will be randomly assigned to either the evolocumab treatment group or the standard treatment group after completing culprit vessel revascularisation. The evolocumab treatment group will receive evolocumab in addition to statin therapy, while the standard treatment group will receive standard statin therapy. At baseline and week 50, patients in the evolocumab treatment group will undergo coronary angiography and OCT imaging to visualise pre-existing non-lesional vessels. The primary end point is the absolute change in average minimum fibrous cap thickness (FCT) from baseline to week 50. Secondary end points include changes in plaque lipid arc, lipid length, macrophage grading, lipid levels and major adverse cardiovascular events during the 1-year follow-up period. ETHICS AND DISSEMINATION: Ethics: this study will adhere to the principles outlined in the Helsinki Declaration and other applicable ethical guidelines. This study protocol has received approval from the Medical Research Ethics Committee of the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital), with approval number 2022-ky214. DISSEMINATION: we plan to disseminate the findings of this study through various channels. This includes publication in peer-reviewed academic journals, presentation at relevant academic conferences and communication to the public, policymakers and healthcare professionals. We will also share updates on the research progress through social media and other online platforms to facilitate the exchange and application of scientific knowledge. Efforts will be made to ensure widespread dissemination of the research results and to have a positive impact on society. TRIAL REGISTRATION NUMBER: ChiCTR2200066675.

Neurologic music therapy for non-fluent aphasia: a systematic review and meta-analysis of randomized controlled trials.

Introduction: The efficacy of neurologic music therapy (NMT) techniques for the treatment of non-fluent aphasia has been widely accepted by the rehabilitation medical community. However, consensus on which dimensions of speech function can be improved by NMT techniques and standardized intervention dosage remains elusive. This study aimed to provide evidence regarding the efficacy of NMT in improving speech function and explore the optimal intervention dose. A systematic review and meta-analysis were conducted to search for randomized clinical trials and open-label trials that evaluated speech functions after NMT. Methods: We searched all papers and reviews published from database inception to July 2023, including PubMed, Cochrane Library, Web of Science, Embase, and CNKI. Statistical analyses were mainly carried out on RevManV5.4.1 and pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in speech functions, determined by calculating the change in speech functions score from baseline to the primary endpoint in the NMT group versus the control arm. Results: A total of 11 studies with 329 patients were included. NMT had a positive effect on repetition ability (SMD = 0.37, 95%CI [0.12, 0.62], p < 0.05), but did not lead to significant differences in naming, comprehension, spontaneous speech, or communication. When the intervention time was >20 h, NMT exhibited a significant advantage at improving repetition ability (SMD = 0.43, 95%CI [0.06, 0.79], p < 0.05). Discussion: This study provides evidence supporting the NMT enhancement of repetition ability in patients with non-fluent aphasia. Future large-sample studies are required to determine the optimal intervention dose of music therapy for different subtypes of non-fluent aphasia. Systematic review registration: PROSPERO, identifier CRD42023470313.

Lipidomic signatures in patients with early-onset and late-onset Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the gestational age of delivery. Patients with preeclampsia have aberrant lipid metabolism. This study aims to compare serum lipid profiles of normal pregnant women with EOPE or LOPE and screening potential biomarkers to diagnose EOPE or LOPE. METHODS: Twenty normal pregnant controls (NC), 19 EOPE, and 19 LOPE were recruited in this study. Untargeted lipidomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to compare their serum lipid profiles. RESULTS: The lipid metabolism profiles significantly differ among the NC, EOPE, and LOPE. Compared to the NC, there were 256 and 275 distinct lipids in the EOPE and LOPE, respectively. Furthermore, there were 42 different lipids between the LOPE and EOPE, of which eight were significantly associated with fetal birth weight and maternal urine protein. The five lipids that both differed in the EOPE and LOPE were DGTS (16:3/16:3), LPC (20:3), LPC (22:6), LPE (22:6), PC (18:5e/4:0), and a combination of them were a potential biomarker for predicting EOPE or LOPE. The receiver operating characteristic analysis revealed that the diagnostic power of the combination for distinguishing the EOPE from the NC and for distinguishing the LOPE from the NC can reach 1.000 and 0.992, respectively. The association between the lipid modules and clinical characteristics of EOPE and LOPE was investigated by the weighted gene co-expression network analysis (WGCNA). The results demonstrated that the main different metabolism pathway between the EOPE and LOPE was enriched in glycerophospholipid metabolism. CONCLUSIONS: Lipid metabolism disorders may be a potential mechanism of the pathogenesis of preeclampsia. Lipid metabolites have the potential to serve as biomarkers in patients with EOPE or LOPE. Furthermore, lipid metabolites correlate with clinical severity indicators for patients with EOPE and LOPE, including fetal birth weight and maternal urine protein levels.

The association of EGFR amplification with aberrant exon 20 insertion report using the cobas EGFR Mutation Test v2.

Determining the exact type of epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation in lung cancer has become important. We found that not all ex20ins mutations reported by cobas EGFR test v2 could be validated by Sanger sequencing even using surgical specimens with high tumor contents. This study aimed to validate the ex20ins results reported by the cobas test and to determine whether there were clinicopathological factors associated with aberrant cobas ex20ins report. In total, 123 cobas-reported cases with ex20ins were retrospectively collected and validated by Sanger sequencing and Idylla assay. Clinicopathological features between ex20ins cobas+/Sanger+ group (n = 71) and cobas+/Sanger- group (n = 52) were compared. The Idylla assay detected ex20ins in 82.6% of cobas+/Sanger+ cases but only in 4.9% of cobas+/Sanger- cases. The cobas+/Sanger- group was significantly associated with higher tumor contents, poorly differentiated patterns, tumor necrosis, and a lower internal control cycle threshold value reported by the Idylla which suggesting the presence of increased EGFR gene copy numbers. EGFR fluorescence in situ hybridization (FISH) revealed the majority of cobas+/Sanger- group had EGFR high copy number gain (16%) or amplification (76%) according to the Colorado criteria. Among cases reported to have concomitant classic EGFR and ex20ins mutations by the cobas, the classic EGFR mutations were all detected by Sanger sequencing and Idylla, while the ex20ins mutations were undetected by Sanger sequencing (0%) or rarely reported by Idylla assay (3%). FISH revealed high EGFR copy number gain (17.9%) and amplification (79.5%) in cases reported having concomitant classic EGFR and ex20ins mutations by the cobas. This study demonstrated an unusually high frequency of EGFR amplification in cases with aberrant cobas ex20ins report which could not be validated by Sanger sequencing or Idylla assay. Ex20ins reported by the cobas test should be validated using other methods especially those reported having concomitant ex20ins and classic EGFR mutations.

Mitochondria-Selective Dicationic Small-Molecule Ligand Targeting G-Quadruplex Structures for Human Colorectal Cancer Therapy.

Mitochondria are important drug targets for anticancer and other disease therapies. Certain human mitochondrial DNA sequences capable of forming G-quadruplex structures (G4s) are emerging drug targets of small molecules. Despite some mitochondria-selective ligands being reported for drug delivery against cancers, the ligand design is mostly limited to the triphenylphosphonium scaffold. The ligand designed with lipophilic small-sized scaffolds bearing multipositive charges targeting the unique feature of high mitochondrial membrane potential (MMP) is lacking and most mitochondria-selective ligands are not G4-targeting. Herein, we report a new small-sized dicationic lipophilic ligand to target MMP and mitochondrial DNA G4s to enhance drug delivery for anticancer. The ligand showed marked alteration of mitochondrial gene expression and substantial induction of ROS production, mitochondrial dysfunction, DNA damage, cellular senescence, and apoptosis. The ligand also exhibited high anticancer activity against HCT116 cancer cells (IC50, 3.4 µM) and high antitumor efficacy in the HCT116 tumor xenograft mouse model (∼70% tumor weight reduction).

Live Cell Imaging and Real-Time Monitoring of Nucleolus Morphology and Mitophagy with a Red Fluorescent and Photostable rRNA-Specific Probe in Human Cancer Cells.

rRNAs are prevalent in living organisms. They are produced in nucleolus and mitochondria and play essential cellular functions. In addition to the primary biofunction in protein synthesis, rRNAs have been recognized as the emerging signaling molecule and drug target for studies on nucleolus morphology, mitochondrial autophagy, and tumor cell malignancy. Currently, only a few rRNA-selective probes have been developed, and most of them encounter the drawbacks of low water solubility, poor nuclear membrane permeability, short emission wavelength, low stability against photobleaching, and high cytotoxicity. These unfavorable properties of rRNA probes limit their potential applications. In the present study, we reported a new rRNA-selective and near-infrared fluorescent turn-on probe, 4MPS-TO, capable of tracking rRNA in live human cancer cells. The real-time monitoring performance in nucleolus morphology and mitochondrial autophagy is demonstrated in HeLa cells. The probe shows great application potential for being used as a rRNA-selective, sensitive, and photostable imaging tool in chemical biology study and drug screening.

Rotor-based image-guided therapy of glioblastoma.

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.

Potential therapeutic role of spermine via Rac1 in osteoporosis: Insights from zebrafish and mice.

Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side effects and high costs, necessitating the development of more effective and safer targeted therapies. Utilizing a zebrafish ( Danio rerio) larval model of osteoporosis, we explored the influence of the metabolite spermine on bone homeostasis. Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption. Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae. At the molecular level, Rac1 was identified as playing a pivotal role in mediating the anti-osteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse ( Mus musculus) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone-strengthening agent. This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

Uptake, translocation, and metabolism of organophosphate esters (OPEs) in plants and health perspective for human: A review.

Plant uptake, accumulation, and transformation of organophosphate esters (OPEs) play vital roles in their geochemical cycles and exposure risks. Here we reviewed the recent research advances in OPEs in plants. The mean OPE concentrations based on dry/wet/lipid weight varied in 4.80-3,620/0.287-26.8/12,000-315,000 ng g-1 in field plants, and generally showed positive correlations with those in plant habitats. OPEs with short-chain substituents and high hydrophilicity, particularly the commonly used chlorinated OPEs, showed dominance in most plant samples, whereas some tree barks, fruits, seeds, and roots demonstrated dominance of hydrophobic OPEs. Both hydrophilic and hydrophobic OPEs can enter plants via root and foliar uptake, and the former pathway is mainly passively mediated by various membrane proteins. After entry, different OPEs undergo diverse subcellular distributions and acropetal/basipetal/intergenerational translocations, depending on their physicochemical properties. Hydrophilic OPEs mainly exist in cell sap and show strong transferability, hydrophobic OPEs demonstrate dominant distributions in cell wall and limited migrations owing to the interception of Casparian strips and cell wall. Additionally, plant species, transpiration capacity, growth stages, commensal microorganisms, and habitats also affect OPE uptake and transfer in plants. OPE metabolites derived from various Phase I transformations and Phase II conjugations are increasingly identified in plants, and hydrolysis and hydroxylation are the most common metabolic processes. The metabolisms and products of OPEs are closely associated with their structures and degradation resistance and plant species. In contrast, plant-derived food consumption contributes considerably to the total dietary intakes of OPEs by human, particularly the cereals, and merits specifical attention. Based on the current research limitations, we proposed the research perspectives regarding OPEs in plants, with the emphases on their behavior and fate in field plants, interactions with plant-related microorganisms, multiple uptake pathways and mechanisms, and comprehensive screening analysis and risk evaluation.

Prediction of fruit characteristics of grafted plants of Camellia oleifera by deep neural networks.

BACKGROUND: Camellia oleifera, an essential woody oil tree in China, propagates through grafting. However, in production, it has been found that the interaction between rootstocks and scions may affect fruit characteristics. Therefore, it is necessary to predict fruit characteristics after grafting to identify suitable rootstock types. METHODS: This study used Deep Neural Network (DNN) methods to analyze the impact of 106 6-year-old grafting combinations on the characteristics of C.oleifera, including fruit and seed characteristics, and fatty acids. The prediction of characteristics changes after grafting was explored to provide technical support for the cultivation and screening of specialized rootstocks. After determining the unsaturated fat acids, palmitoleic acid C16:1, cis-11 eicosenoic acid C20:1, oleic acid C18:1, linoleic acid C18:2, linolenic acid C18:3, kernel oil content, fruit height, fruit diameter, fresh fruit weight, pericarp thickness, fresh seed weight, and the number of fresh seeds, the DNN method was used to calculate and analyze the model. The model was screened using the comprehensive evaluation index of Mean Absolute Error (MAPE), determinate correlation R2 and and time consumption. RESULTS: When using 36 neurons in 3 hidden layers, the deep neural network model had a MAPE of less than or equal to 16.39% on the verification set and less than or equal to 13.40% on the test set. Compared with traditional machine learning methods such as support vector machines and random forests, the DNN method demonstrated more accurate predictions for fruit phenotypic characteristics, with MAPE improvement rates of 7.27 and 3.28 for the 12 characteristics on the test set and maximum R2 improvement values of 0.19 and 0.33. In conclusion, the DNN method developed in this study can effectively predict the oil content and fruit phenotypic characteristics of C. oleifera, providing a valuable tool for predicting the impact of grafting combinations on the fruit of C. oleifera.

[Effects of Microplastics on the Leaching of Nutrients and Cadmium from Soil].

The environmental effects of microplastics, which are considered a type of emerging contaminants, have attracted increasing concern due to their small size, large specific surface area, strong adsorption capacity, and low degradability. Microplastics can change soil properties and affect the migration ability of nutrients and pollutants in soil, but their effects on the leaching of soil nutrients and heavy metals have not been sufficiently studied. A soil column leaching experiment was conducted to explore the effects of polystyrene (PS) and polylactic acid (PLA) microplastics at different mass fractions (0%, 0.2%, and 2%) on the leaching of nutrients and cadmium under simulated rainfall scenarios. The results showed that increasing rainfall intensity enhanced the leaching of nutrients and cadmium from soil. During downpour conditions, 2% PS significantly increased the leaching of total nitrogen and the content of available phosphorus in soil and reduced the leaching of inorganic phosphorus and the content of ammonium nitrogen in the soil, whereas it increased the content of available potassium during heavy rain. By comparison, 2% PLA reduced the leaching of nitrate nitrogen during heavy rain and intense rainfall and decreased the content of ammonium nitrogen in soil during intense rainfall and downpour conditions and the content of total nitrogen in soil during downpours. In addition, 0.2% PLA significantly increased cadmium leaching during downpours. To conclude, the effects of microplastics on the leaching of nutrients and cadmium were dependent on the type and concentration of microplastics, as well as the rainfall level. Our findings showed that the microplastics derived from both nondegradable PS and biodegradable PLA could affect the leaching of nutrients and heavy metals from soil.

RNA sequencing and proteomic profiling reveal alterations by MPTP in chronic stomach mucosal injury in tree shrew Chinese (Tupaia belangeri chinensis).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that can cause gastrointestinal ulcers by affecting dopamine levels. Therefore, MPTP has been considered a toxic substance that causes gastric ulcer disease in experimental animals. In this study, tree shrews were used as the animal model of gastric mucosa injury, and MPTP was intraperitoneally injected at a lower MPTP dosage 2 mg/kg/day for 13 weeks, while tree shrews were not injected as the control group. Under the light microscope, local congestion or diffuse bleeding points of gastric mucosa and multiple redness and swelling bleeding symptoms on the inner wall were observed in the treatment group, as well as immune cell infiltration was found in HE staining, but no such phenomenon was observed in the control group. In order to explore the molecular basis of changes in MPTP induced gastric mucosa injury, the transcriptome and proteome data of gastric mucosa were analyzed. We observed significant differences in mRNA and protein expression levels under the influence of MPTP. The changes in mRNA and proteins are related to increased immune infiltration, cellular processes and angiogenesis. More differentially expressed genes play a role in immune function, especially the candidate genes RPL4 and ANXA1 with significant signal and core role. There are also differentially expressed genes that play a role in mucosal injury and shedding, especially candidate genes GAST and DDC with certain signaling and corresponding functions. Understanding the factors and molecular basis that affect the expression of related genes is crucial for coping with Emotionality gastric mucosa injury disease and developing new treatment methods to establish the ability to resist disease.

Temporal dynamics of stomatal regulation and carbon- and water-related traits for a native tree species in low subtropical China.

Stomata are pivotal in modulating water and carbon processes within plants. However, our understanding of the temporal dynamics of water- and carbon-related traits, as influenced by stomatal behavior, remains limited. Here, we explore how stomatal regulation behavior and water- and carbon-related traits vary with changing environments by examining the seasonal variations in these traits of the native tree species Schima superba in low subtropical China. In February, April, and July of 2022, a series of water- and carbon-related traits were measured in the leaves and stems. The results showed that S. superba exhibited isohydric behavior in February when the soil dried out and vapor pressure deficit (VPD) was lower but anisohydric behavior in April and July when the soil was wetter and VPD was higher. In February, NSC and their components increased, and a relatively large contribution of soluble sugars to the change in NSC was observed. In the branches and phloem, NSC and their components displayed a relatively high monthly variability, suggesting their role in maintaining carbon balance within the trees. Conversely, the NSC in the leaves demonstrated minimal monthly variability. The specific leaf area, as well as the concentration of nitrogen (N) and phosphorus (P) per unit mass in leaves and the cumulative stem water release, exhibited a decrease with a reduction in soil water potential. Interestingly, the hydraulic conductivity remained consistent throughout this process. Furthermore, the relatively low monthly growth rate observed in February could suggest a carbon sink limitation. In conclusion, the increased NSC and decreased water status of S. superba under relatively stressed soil conditions indicated a trade-off between water and carbon storage. Our findings enhance our comprehension of the dynamics and regulation of water and carbon status in forests, thereby advancing the development of plant carbon and water process models under climate change scenarios.

Simultaneous Interfacial Defect Passivation and Bottom-Up Excess PbI2 Management via Rubidium Chloride in Highly Efficient Perovskite Solar Cells with Suppressed Hysteresis.

In halide perovskite solar cells (PSCs), moderate lead iodide (PbI2) can enhance device efficiency by providing some passivation effects, but extremely active PbI2 leads to the current density-voltage hysteresis effect and device instability. In addition, defects distributed on the buried interface of tin oxide (SnO2)/perovskite will lead to the photogenerated carrier recombination. Here, rubidium chloride (RbCl) is introduced at the buried SnO2/perovskite interface, which not only acts as an interfacial passivator to interact with the uncoordinated tin ions (Sn4+) and fill the oxygen vacancy on the SnO2 surface but also converts PbI2 into an inactive (PbI2)2RbCl compound to stabilize the perovskite phase via a bottom-up evolution effect. These synergistic effects deliver a champion PCE of 22.13% with suppressed hysteresis for the W RbCl PSCs, in combination with enhanced environmental and thermal stability. This work demonstrates that the interfacial defect passivation and bottom-up excess PbI2 management using RbCl modifiers are promising strategies to address the outstanding challenges associated with PSCs.

Uptake mechanism, translocation, and transformation of organophosphate esters in water hyacinth (Eichhornia crassipes): A hydroponic study.

Owing to their dominant wastewater origin, bioavailability, and toxicity, the occurrence and behavior of organophosphate esters (OPEs) in aquatic systems have attracted considerable attention over the past two decades. Aquatic plants can accumulate and metabolize OPEs in water, thereby playing an important role in their behavior and fate in waterbodies. However, their uptake, translocation and transformation mechanisms in plants remain incompletely characterized. We investigated the accumulation and transformation of OPEs in water hyacinth (Eichhornia crassipes) through a series of hydroponic experiments using three representative OPEs, tris(2-chloroethyl) phosphate (TCEP), tris(2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPP). These OPEs can not only be adsorbed onto and enter plant roots via passive diffusion pathways, which are facilitated by anion channels and/or aquaporins, but also can return to the solution when concentration gradients exist. After entry, hydrophilic TCEP showed a dominant distribution in the cell sap, strong acropetal transportability, and rapid translocation rate, whereas hydrophobic TPP was mostly retained in the root cell wall and therefore demonstrated weak acropetal transportability; TBEP with moderate hydrophilicity remained in the middle. All these OPEs can be transformed into diesters, which presented higher proportions in the cell sap and therefore have stronger acropetal transferability than their parent OPEs. TCEP exhibits the lowest biodegradability, followed by TPP and TBEP. These OPEs exerted apparent effects on plant growth, photosynthesis, and the diversity and composition of the rhizosphere microbial community.

Permanent vs Transient Congenital Hypothyroidism in Chinese Children: Physical Growth and Predictive Nomogram.

CONTEXT: Few reliable markers are available to distinguish transient congenital hypothyroidism (TCH) and permanent congenital hypothyroidism (PCH). Additionally, the differences in growth between TCH and PCH remain unclear. OBJECTIVE: To investigate the growth of children with TCH and PCH and develop a nomogram for early differentiation of these forms. METHODS: This retrospective study included children with TCH or PCH. The predictive efficacy of the prognostic predictors was analyzed using receiver operating characteristic analysis. Multivariate prediction models were developed. Measurements of growth were compared between groups. RESULTS: Patients with TCH had lower initial thyroid-stimulating hormone (TSH) than those with PCH at newborn screening (NBS). The supplementary dose of levothyroxine (L-T4) gradually decreased with age in TCH but not in PCH. The area under the curve (AUC) values of the initial TSH, L-T4 dose at 1 year of age, and L-T4 dose at 2 years of age for distinguishing TCH from PCH were 0.698, 0.71, and 0.879, respectively. The predictive efficacy of the multivariate models at 1 and 2 years of age improved, with AUC values of 0.752 and 0.922, respectively. A nomogram was built based on the multivariate model at 1 year of age. The growth did not differ between children with TCH and those with PCH. However, at 1 year of age, girls with CH exhibited higher z-scores in terms of height and weight than boys with CH. CONCLUSION: TSH at NBS and L-T4 doses during treatment can be used to distinguish between PCH and TCH early in life, and the predictive efficacy can be improved using multivariable models with a visualized nomogram. At 3 years of age, patients with TCH and PCH showed similar growth.

Research progress of extracellular vesicles in the treatment of ovarian diseases (Review).

The ovary is an essential reproductive organ in the female organism and its development seriously affects the physical and mental health of female patients. Ovarian diseases include ovarian cancer, premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). Women should pay attention to the most effective treatments for this condition because it is one of the most prevalent gynecological illnesses at present. Extracellular vesicles (EVs), which are smaller vesicles that mediate the exchange of cellular information, include the three categories of exosomes, microvesicles and apoptotic bodies. They are able to transport proteins, RNA and other substances to adjacent or distal cells, thus allowing cellular and tissue homeostasis to be maintained. Numerous previous studies have revealed that EVs are crucial for the treatment of ovarian diseases. They are known to transport its contents to ovarian cancer cells as well as other ovarian cells such as granulosa cells, affecting the development of ovarian disease processes. Therefore, this extracellular vesicle may be involved as a target in the therapeutic process of ovarian disease and may have great potential in the treatment of ovarian disease. In the present review, the role of EVs in the development of three ovarian diseases, including ovarian cancer, POI and PCOS, was mainly summarizes. It is expected that this will provide some theoretical support for the treatment of ovarian disease.

Simultaneous real-time detection of fractional exhaled nitric oxide and end-tidal carbon dioxide by quantum cascade laser absorption spectroscopy.

The simultaneous detection of fractional exhaled nitric oxide (FeNO) and end-tidal carbon dioxide (ETCO2) is of great importance for the distinguishing and diagnosis of asthma and chronic obstructive pulmonary disease (COPD), providing more comprehensive information on respiratory disorders. This work demonstrates a simultaneous ETCO2 and FeNO detection system based on quantum cascade laser absorption spectroscopy (QCLAS) technology was presented. The system employs wavelength modulation spectroscopy (WMS) technology and the Herriott multi-pass cell, achieving a detection limit of 2.82 ppb for nitric oxide (NO) and 0.05 % for carbon dioxide (CO2). Real-time exhalation measurements were performed on volunteers with varying ETCO2 and FeNO levels, and the results of the test can accurately distinguish whether the corresponding volunteer was healthy, had asthma or COPD. The effect of exhalation flow rate on the concentration of the two gases was explored. A range of expiratory flow rates were tested in the flow rate interval from 1 to 4 L/min, and there was always an inverse relationship between expiratory flow rate and FeNO concentration, but flow rate changes did not affect ETCO2 concentration. The results indicate that this detection system can simultaneously and effectively measure ETCO2 and FeNO concentrations in real-time.

Engineered platelet cell motors for boosted cancer radiosensitization.

Design of engineered cells to target and deliver nanodrugs to the hard-to-reach regions has become an exciting research area. However, the limited penetration and retention of cell-based carriers in tumor tissue restricted their therapeutic efficiency. Inspired by the enhanced delivery behavior of mobile micro/nanomotors, herein, urease-powered platelet cell motors (PLT@Au@Urease) capable of active locomotion, tumor targeting, and radiosensitizers delivery were designed for boosting radiosensitization. The engineered platelet cell motors were constructed by in situ synthesis and loading of radiosensitizers gold nanoparticles in platelets, and then conjugation with urease as the engine. Under physiological concentration of urea, thrust around PLT@Au@Urease motors can be generated via the biocatalytic reactions of urease, leading to rapid tumor cell targeting and enhanced cellular uptake of radiosensitizers. Encouragingly, in comparison with engineered PLT without propulsion capability (PLT@Au), the self-propelled PLT@Au@Urease motors could significantly increase intracellular ROS level and exacerbate nuclear DNA damage induced by γ-radiation, resulting in a remarkably high sensitization enhancement rate (1.89) than that of PLT@Au (1.08). In vivo experiments with 4 T1-bearing mice demonstrated that PLT@Au@Urease in combination with radiation therapy possessed good antitumor performance. Such an intelligent cell motor would provide a promising approach to enhance radiosensitization and broaden the applications of cell motor-based delivery systems.