A comprehensive evaluation of influencing factors of neonicotinoid insecticides (NEOs) in farmland soils across China: First focus on film mulching.

Neonicotinoid insecticide (NEO) residues in agricultural soils have concerning and adverse effects on agroecosystems. Previous studies on the effects of farmland type on NEOs are limited to comparing greenhouses with open fields. On the other hand, both NEOs and microplastics (MPs) are commonly found in agricultural fields, but their co-occurrence characteristics under realistic fields have not been reported. This study grouped farmlands into three types according to the covering degree of the film, collected 391 soil samples in mainland China, and found significant differences in NEO residues in the soils of the three different farmlands, with greenhouse having the highest NEO residue, followed by farmland with film mulching and farmland without film mulching (both open fields). Furthermore, this study found that MPs were significantly and positively correlated with NEOs. As far as we know this is the first report to disclose the association of film mulching and MPs with NEOs under realistic fields. Moreover, multiple linear regression and random forest models were used to comprehensively evaluate the factors influencing NEOs (including climatic, soil, and agricultural indicators). The results indicated that the random forest model was more reliable, with MPs, farmland type, and total nitrogen having higher relative contributions.

Spatial distribution, compositional characteristics, and source apportionment of legacy and novel per- and polyfluoroalkyl substances in farmland soil: A nationwide study in mainland China.

China, as one of the largest global producers and consumers of per- and poly-fluoroalkyl substances (PFASs), faces concerning levels of PFAS pollution in soil. However, knowledge of their occurrence in agricultural soils of China on the national scale remains unknown. Herein, the first nationwide survey was done by collecting 352 soil samples from 31 provinces in mainland China. The results indicated that the Σ24PFASs concentrations were 74.3 - 24880.0 pg/g, with mean concentrations of PFASs in decreasing order of legacy PFASs > emerging PFASs > PFAS precursors (640.2 pg/g, 340.7 pg/g, and 154.9 pg/g, respectively). The concentrations in coastal eastern China were distinctly higher than those in inland regions. Tianjin was the most severely PFASs-contaminated province because of rapid urban industrialization. This study further compared the PFAS content in monoculture and multiple cropping farmland soils, finding the concentrations of PFASs were high in soils planted with vegetable and fruit monocultures. Moreover, a positive matrix factorization (PMF) model was employed to identify different sources of PFASs. Fluoropolymer industries and aqueous film-forming foams were the primary contributors. The contributions from different emission sources varied across the seven geographical regions. This study provides new baseline data for prevention and control policies for reducing pollution.

Reliability and validity of the Chinese version of the sunlight exposure questionnaire.

Objective: This study aimed to translate and validate the reliability and validity of the Chinese version of the Philippines Sunlight Exposure Questionnaire. Methods: A total of 392 Chinese individuals aged at least 18 years, residing in various cities in Sichuan province for at least 1 year, were recruited. The reliability of the Chinese version of the questionnaire was measured through internal consistency, split-half reliability, and retest reliability, while validity was determined using the content validity index and the structure validity index. Results: The Chinese version of the Sunlight Exposure Questionnaire, which includes 19 items covering 5 factors, demonstrated McDonald's omega coefficient of 0.788. The split-half reliability of the questionnaire was 0.823, and the retest reliability was 0.940. The content validity index (S-CVI) was 0.952. The five-factor structure, supported by eigenvalues, explained 66.2% of the total variance. Confirmatory factor analysis indicated favorable model fit. Results: The chi-square value degrees of freedom ratio (χ2/df) = 1.852, the goodness-of-fit index (GFI) = 0.938, the normed fit index (NFI) = 0.922, the incremental fit index (IFI) = 0.962, the comparative fit index (CFI) = 0.962, the Tucker-Lewis index (TLI) = 0.952, and root mean square error of approximation (RMSEA) = 0.047. The indicators of the fit of the model were within reasonable bounds. Conclusion: The Chinese version of the Sunlight Exposure Questionnaire shows validity and good reliability for assessing sun exposure among adults in a Chinese cultural context.

Phase transition in WSe2-xTex monolayers driven by charge injection and pressure: a first-principles study.

Alloying strategies permit new probes for governing structural stability and semiconductor-semimetal phase transition of transition metal dichalcogenides (TMDs). However, the possible structure and phase transition mechanism of the alloy TMDs, and the effect of an external field, have been still unclear. Here, the enrichment of the Te content in WSe2-xTex monolayers allows for coherent structural transition from the H phase to the T' phase. The crystal orbital Hamiltonian population (COHP) uncovers that the bonding state of the H phase approaches the high-energy domain near the Fermi level as the Te concentration increases, posing a source of structural instability followed by a weakened energy barrier for the phase transition. In addition, the structural phase transition driven by charge injection opens up new possibilities for the development of phase-change devices based on atomic thin films. For WSe2-xTex monolayers with the H phase as the stable phase, the critical value of electron concentration triggering the phase transition decreases with an increase in the x value. Furthermore, the energy barrier from the H phase to the T' phase can be effectively reduced by applying tensile strain, which could favor the phase switching in electronic devices. This work provides a critical reference for controllable modulation of phase-sensitive devices from alloy materials with rich phase characteristics.

A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.

Outcome of arthroscopic triple release combined with rotator cuff repair in the treatment of rotator cuff injury combined with frozen shoulder.

Objective: To investigate the effect of arthroscopic triple release combined with rotator cuff repair in the treatment of rotator cuff injury combined with frozen shoulder and its influence on the range of motion and pain score of shoulder joint, and the levels of serum pain mediators. Methods: This was prospective study. A total of 132 patients with rotator cuff injury combined with frozen shoulder admitted to The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine from December 2020 to December 2022 were prospectively selected and divided into two groups according to the random number table method: control group (n=67) and observation group (n=65). Patients in the control group were treated with arthroscopic rotator cuff repair alone, while those in the observation group were treated with arthroscopic triple release combined with rotator cuff repair, and the surgical effects of the two groups were compared. Results: Three months after treatment, the external rotation, internal rotation, abduction, forward flexion, ß-endorphin(ß-EP), prostagranin E2 (PGE2) and substance P(SP)in the observation group were better than those in the control group (P<0.05), while the weight-bearing strength of the affected limb in internal rotation, external rotation and forward flexion was higher than that of the control group(P<0.05). Meanwhile, the Visual Analogue Scale (VAS) score of the observation group was lower than that of the control group at one month and three months after treatment, while the University of California at Los Angeles shoulder rating scale (UCLA) score and Constant-Murley Score (CMS) were higher than those of the control group (P< 0.05). Conclusion: Arthroscopic triple release combined with rotator cuff repair improves various effects for patients with rotator cuff injury combined with frozen shoulder, such as ameliorating the muscle strength of the affected limb and improving the level of pain mediators.

Effects of light therapy on sleep and circadian rhythm in older type 2 diabetics living in long-term care facilities: a randomized controlled trial.

Background: Light influences the secretion of melatonin in the body and regulates circadian rhythms, which play an important role in sleep and mood. The light level of rooms in long-term care facilities is usually far below the threshold required to regulate the body's circadian rhythm, and insufficient light can easily lead to sleep and mood disturbances among older residents in nursing homes. Therefore, the objective of this study was to investigate the effects of light therapy on sleep and circadian rhythm in older adults with type 2 diabetes residing in long-term care facilities. Methods: This study was a prospective, single-blind, randomized controlled trial. Participants were randomly assigned to either the light therapy (LT) group or the control group and received the intervention for four weeks. Primary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and objective sleep parameters recorded by a sleep monitoring bracelet, Morningness-Eveningness Questionnaire (MEQ). The secondary outcome included glycated serum protein (GSP). Data was collected at three time points: at baseline (T0), immediate post-treatment (T1), and 4-week follow-up (T2). A linear mixed model analysis was used to analyzed the data. Results: We enrolled 45 long-term care residents. Compared with the control group, significant reductions in PSQI scores were observed at T1 and T2. At T2, the sleep score of objective sleep parameters was significantly higher in the LT group compared to the control group. Additionally, compared to the baseline T0, MEQ scores were significantly lower in the LT group at T1 and T2, with no significant difference in the control group. There was no significant difference between groups in glycated serum protein values at T1 and T2. However, compared to T0, glycated serum protein values decreased in the LT group while increased in the control group at T2. Conclusion: Light therapy had a positive effect on subjective sleep quality and circadian rhythm time type in long-term care residents with type 2 diabetes, and had a possible delayed effect on objective sleep. However, no discernible alterations in blood glucose levels were detected in this study.

Pollution characteristics and affecting factors of phthalate esters in agricultural soils in mainland China.

Phthalate esters (PAEs), the most commonly produced and used plasticizers, are widely used in plastic products and agroecosystems, posing risks to agricultural products and human health. However, current research on PAE pollution characteristics in agricultural soils in China is not comprehensive; affecting factors and relationships with microplastics and plasticizer organophosphate esters have not been sufficiently considered. In this study, farmland soil samples were collected with field questionnaires on a national scale across mainland China. The results showed that the detection rate of PAEs was 100% and the Σ16PAEs concentrations were 23.5 - 903 µg/kg. The level of PAEs was highest in the greenhouse, and significantly higher than that in mulched farmland (p < 0.05). The PAE concentration in northwestern China was the lowest among different physical geographic zones. PAEs in farmlands posed a low cancer risk to Chinese people. PAE pollution in farmlands was significantly (p < 0.05) affected by agronomic measures (such as disposal method), environmental factors, and socioeconomic factors. Overall, PAEs were significantly and positively correlated (p < 0.05) with organophosphate esters but not with microplastics. This study aims to provide scientific data for relevant prevention and control policies, as well as actionable recommendations for pollution reduction.

CNN-based multi-modal radiomics analysis of pseudo-CT utilization in MRI-only brain stereotactic radiotherapy: a feasibility study.

BACKGROUND: Pseudo-computed tomography (pCT) quality is a crucial issue in magnetic resonance image (MRI)-only brain stereotactic radiotherapy (SRT), so this study systematically evaluated it from the multi-modal radiomics perspective. METHODS: 34 cases (< 30 cm³) were retrospectively included (2021.9-2022.10). For each case, both CT and MRI scans were performed at simulation, and pCT was generated by a convolutional neural network (CNN) from planning MRI. Conformal arc or volumetric modulated arc technique was used to optimize the dose distribution. The SRT dose was compared between pCT and planning CT with dose volume histogram (DVH) metrics and gamma index. Wilcoxon test and Spearman analysis were used to identify key factors associated with dose deviations. Additionally, original image features were extracted for radiomic analysis. Tumor control probability (TCP) and normal tissue complication probability (NTCP) were employed for efficacy evaluation. RESULTS: There was no significant difference between pCT and planning CT except for radiomics. The mean value of Hounsfield unit of the planning CT was slightly higher than that of pCT. The Gadolinium-based agents in planning MRI could increase DVH metrics deviation slightly. The median local gamma passing rates (1%/1 mm) between planning CTs and pCTs (non-contrast) was 92.6% (range 63.5-99.6%). Also, differences were observed in more than 85% of original radiomic features. The mean absolute deviation in TCP was 0.03%, and the NTCP difference was below 0.02%, except for the normal brain, which had a 0.16% difference. In addition, the number of SRT fractions and lesions, and lesion morphology could influence dose deviation. CONCLUSIONS: This is the first multi-modal radiomics analysis of CNN-based pCT from planning MRI for SRT of small brain lesions, covering dosiomics and radiomics. The findings suggest the potential of pCT in SRT plan design and efficacy prediction, but caution needs to be taken for radiomic analysis.

Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.

Zero-Shot Medical Image Translation via Frequency-Guided Diffusion Models.

Recently, the diffusion model has emerged as a superior generative model that can produce high quality and realistic images. However, for medical image translation, the existing diffusion models are deficient in accurately retaining structural information since the structure details of source domain images are lost during the forward diffusion process and cannot be fully recovered through learned reverse diffusion, while the integrity of anatomical structures is extremely important in medical images. For instance, errors in image translation may distort, shift, or even remove structures and tumors, leading to incorrect diagnosis and inadequate treatments. Training and conditioning diffusion models using paired source and target images with matching anatomy can help. However, such paired data are very difficult and costly to obtain, and may also reduce the robustness of the developed model to out-of-distribution testing data. We propose a frequency-guided diffusion model (FGDM) that employs frequency-domain filters to guide the diffusion model for structure-preserving image translation. Based on its design, FGDM allows zero-shot learning, as it can be trained solely on the data from the target domain, and used directly for source-to-target domain translation without any exposure to the source-domain data during training. We evaluated it on three cone-beam CT (CBCT)-to-CT translation tasks for different anatomical sites, and a cross-institutional MR imaging translation task. FGDM outperformed the state-of-the-art methods (GAN-based, VAE-based, and diffusion-based) in metrics of Fréchet Inception Distance (FID), Peak Signal-to-Noise Ratio (PSNR), and Structural Similarity Index Measure (SSIM), showing its significant advantages in zero-shot medical image translation.

Characteristics of dissolved organic matter (DOM) in Chinese farmland soils under different climate zone types: A molecular perspective.

Interactions between dissolved organic matter (DOM) and surrounding environments are highly complex. Understanding DOM at the molecular level can contribute to the management of soil pollution and safeguarding agricultural fields. Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) has enabled a molecular-level understanding of DOM. Accordingly, in this study, we investigated soil samples from 27 different regions of mainland China with various soil types and climatic characteristics. Based on the geographical features of the four typical climatic zones in mainland China (temperate monsoon, temperate continental, subtropical monsoon, and Qinghai-Tibet Plateau climates), we employed high-resolution mass spectrometry to determine the molecular diversity of DOM under different climatic conditions. The results indicated that lignin and tannin-like substances were the most active categories of DOM in the soils. Collectively, the composition and unsaturation of DOM molecules are influenced by sunlight, precipitation, temperature, and human activity. All climatic regions contained a substantial number of characteristic molecules, with CHO and CHON constituting over 80%, and DOM containing nitrogen and sulfur was relatively more abundant in the monsoon regions. The complex composition of DOM incorporates various active functional groups, such as -NO2 and -ONO2. Furthermore, soil DOM in the monsoon regions showed higher unsaturation and facilitated various (bio) biochemical reactions in the soil.

Effects of tirofiban on large vessel occlusion stroke are modified by etiology and renal function.

OBJECTIVE: Renal function can modify the outcomes of large vessel occlusion (LVO) stroke across stroke etiologies in disparate degrees. The presence of renal function deficit can also impair the pharmacokinetics of tirofiban. Hence, this study aimed to investigate the roles of renal function in determining efficacy and safety of intravenous tirofiban before endovascular treatment (EVT) for acute ischemic stroke patients with large vessel occlusion (LVO). METHODS: This study was a post hoc exploratory analysis of the RESCUE-BT trial. The primary outcome was the proportion of patients achieving functional independence (modified Rankin scale 0-2) at 90 days, and the primary safety outcome was the rate of symptomatic intracranial hemorrhage (sICH). RESULTS: Among 908 individuals with available serum creatinine, decreased estimated glomerular filtration rate (eGFR) status was noted more commonly in patients with cardioembolic stroke (CE), while large artery atherosclerosis (LAA) was predominant in patients with normal renal function. In LAA with normal renal function, tirofiban was associated with higher rates of functional independence at 90 days (41.67% vs 59.80%, p = 0.003). However, for LVO patients with renal dysfunction, tirofiban did not improve functional outcomes for any of the etiologies (LAA, p = 0.876; CE, p = 0.662; others, p = 0.894) and significantly increased the risk of sICH among non-LAA patients (p = 0.020). Mediation analysis showed tirofiban reduced thrombectomy passes (12.27%) and drug/placebo to recanalization time (14.25%) mediated its effects on functional independence. CONCLUSION: This present study demonstrated the importance of evaluating renal function before administering intravenous tirofiban among patients with LVO who are planned to undergo EVT.

Study on the efficacy, safety, and biomarkers of nusinersen in type II and III spinal muscular atrophy in children.

Introduction/aims: The time span for the approval of nusinersen to treat SMA remains short. Most studies on the efficacy and safety of this drug within clinical trials, are lacking real-world research data. This study is based on real-world studies of SMA patients in children with type II and III SMA and is committed to objectively evaluating the effectiveness and safety of this drug. Methods: A retrospective analysis was conducted on the clinical data of 18 children with type II and III SMA from January 2022 to June 2023. The motor function assessment scale, SMN protein, platelet, liver and kidney function, and other laboratory indicators of all patients before and after treatment were collected for statistical analysis. Results: After load dose treatment (after 64 days of treatment), compared with baseline, the Revised Upper Limb Module (RULM) of SMA patients showed significant improvement (improvement rate: 44%), confirming the short-term effectiveness of the drug. The increase in cerebrospinal fluid SMN protein was greater in patients with significant improvement in motor function than in patients without improvement in motor function. Compared with baseline, there was no significant increase in AST and ALT levels in SMA patients, indicating that the drug had almost no effect on the liver. After each treatment, thrombocytopenia and partial urinary protein positivity may occur, but it could recover before the next treatment. This indicates that nusinersen is potentially harmful to platelet and renal function, although the effect is weak and reversible. Discussion: Nusinersen has shown good efficacy and overall safety, but platelets and urinary protein are still indicators that require long-term monitoring. The increase in cerebrospinal fluid SMN protein was greater in patients with significant improvement in motor function than in patients without improvement in motor function.

A Zinc Oxide Nanowire-Modified Mineralized Collagen Scaffold Promotes Infectious Bone Regeneration.

Bone infection poses a major clinical challenge that can hinder patient recovery and exacerbate postoperative complications. This study has developed a bioactive composite scaffold through the co-assembly and intrafibrillar mineralization of collagen fibrils and zinc oxide (ZnO) nanowires (IMC/ZnO). The IMC/ZnO exhibits bone-like hierarchical structures and enhances capabilities for osteogenesis, antibacterial activity, and bacteria-infected bone healing. During co-cultivation with human bone marrow mesenchymal stem cells (BMMSCs), the IMC/ZnO improves BMMSC adhesion, proliferation, and osteogenic differentiation even under inflammatory conditions. Moreover, it suppresses the activity of Gram-negative Porphyromonas gingivalis and Gram-positive Streptococcus mutans by releasing zinc ions within the acidic infectious microenvironment. In vivo, the IMC/ZnO enables near-complete healing of infected bone defects within the intricate oral bacterial milieu, which is attributed to IMC/ZnO orchestrating M2 macrophage polarization, and fostering an osteogenic and anti-inflammatory microenvironment. Overall, these findings demonstrate the promise of the bioactive scaffold IMC/ZnO for treating bacteria-infected bone defects.

Self-promoted electroactive biomimetic mineralized scaffolds for bacteria-infected bone regeneration.

Infected bone defects are a major challenge in orthopedic treatment. Native bone tissue possesses an endogenous electroactive interface that induces stem cell differentiation and inhibits bacterial adhesion and activity. However, traditional bone substitutes have difficulty in reconstructing the electrical environment of bone. In this study, we develop a self-promoted electroactive mineralized scaffold (sp-EMS) that generates weak currents via spontaneous electrochemical reactions to activate voltage-gated Ca2+ channels, enhance adenosine triphosphate-induced actin remodeling, and ultimately achieve osteogenic differentiation of mesenchymal stem cells by activating the BMP2/Smad5 pathway. Furthermore, we show that the electroactive interface provided by the sp-EMS inhibits bacterial adhesion and activity via electrochemical products and concomitantly generated reactive oxygen species. We find that the osteogenic and antibacterial dual functions of the sp-EMS depend on its self-promoting electrical stimulation. We demonstrate that in vivo, the sp-EMS achieves complete or nearly complete in situ infected bone healing, from a rat calvarial defect model with single bacterial infection, to a rabbit open alveolar bone defect model and a beagle dog vertical bone defect model with the complex oral bacterial microenvironment. This translational study demonstrates that the electroactive bone graft presents a promising therapeutic platform for complex defect repair.

Pretreatment patient-specific quality assurance prediction based on 1D complexity metrics and 3D planning dose: classification, gamma passing rates, and DVH metrics.

PURPOSE: Highly modulated radiotherapy plans aim to achieve target conformality and spare organs at risk, but the high complexity of the plan may increase the uncertainty of treatment. Thus, patient-specific quality assurance (PSQA) plays a crucial role in ensuring treatment accuracy and providing clinical guidance. This study aims to propose a prediction model based on complexity metrics and patient planning dose for PSQA results. MATERIALS AND METHODS: Planning dose, measurement-based reconstructed dose and plan complexity metrics of the 687 radiotherapy plans of patients treated in our institution were collected for model establishing. Global gamma passing rate (GPR, 3%/2mm,10% threshold) of 90% was used as QA criterion. Neural architecture models based on Swin-transformer were adapted to process 3D dose and incorporate 1D metrics to predict QA results. The dataset was divided into training (447), validation (90), and testing (150) sets. Evaluation of predictions was performed using mean absolute error (MAE) for GPR, planning target volume (PTV) HI and PTV CI, mean absolute percentage error (MAPE) for PTV D95, PTV D2 and PTV Dmean, and the area under the receiver operating characteristic (ROC) curve (AUC) for classification. Furthermore, we also compare the prediction results with other models based on either only 1D or 3D inputs. RESULTS: In this dataset, 72.8% (500/687) plans passed the pretreatment QA under the criterion. On the testing set, our model achieves the highest performance, with the 1D model slightly surpassing the 3D model. The performance results are as follows (combine, 1D, and 3D transformer): The AUCs are 0.92, 0.88 and 0.86 for QA classification. The MAEs of prediction are 0.039, 0.046, and 0.040 for 3D GPR, 0.018, 0.021, and 0.019 for PTV HI, and 0.075, 0.078, and 0.084 for PTV CI. Specifically, for cases with 3D GPRs greater than 90%, the MAE could achieve 0.020 (combine). The MAPE of prediction is 1.23%, 1.52%, and 1.66% for PTV D95, 2.36%, 2.67%, and 2.45% for PTV D2, and 1.46%, 1.70%, and 1.71% for PTV Dmean. CONCLUSION: The model based on 1D complexity metrics and 3D planning dose could predict pretreatment PSQA results with high accuracy and the complexity metrics play a leading role in the model. Furthermore, dose-volume metric deviations of PTV could be predicted and more clinically valuable information could be provided.

Application of non-invasive prenatal testing in screening chromosomal aberrations in pregnancies with different nuchal translucency cutoffs.

OBJECTIVE: To investigate the efficiency of non-invasive prenatal testing (NIPT) in cases with different cutoffs of nuchal translucency (NT). METHODS: The study retrospectively analyses pregnancies with NT ≥ 2.5 mm who underwent NIPT. Results of NT, NIPT, chromosomal diagnostic and pregnancy outcomes were collected. RESULTS: Study group was composed of 1470 single pregnancies, including 864 with NT 2.5-2.9 mm, 350 with NT 3.0-3.4 mm and 256 with NT ≥ 3.5 mm. Non-significant differences were found in the positive predictive value (PPV) of NIPT between different cutoffs of NT. There was one false positive case with NT 4.3 mm, screening for 47,XYY in NIPT showed normal in diagnostic testing. For cases with normal NIPT results, the residual risk is 1:20 (5%, 95%CI: 0.1-10.1%) in fetuses with NT 3.0-3.4 mm and 1:15 (6.5%, 95%CI: 1.4%-11.5%) in fetuses with NT ≥ 3.5 mm. These false negative cases included one trisomy 21, seven pathogenic CNVs, one uniparental disomy and one single gene disorders. CONCLUSION: Our findings demonstrated that the PPV of NIPT for screening chromosomal aberrations were similarly in different NT cutoffs, while false positive case does exist. After normal in NIPT, risk for chromosomal aberrations remained, especially pathogenic CNV and even common trisomy. Therefore, prenatal diagnosis was recommended and CMA was suggested to apply in pregnancies with NT ≥ 3.0 mm.

Deep Learning-Predicted Dihydroartemisinin Rescues Osteoporosis by Maintaining Mesenchymal Stem Cell Stemness through Activating Histone 3 Lys 9 Acetylation.

Maintaining the stemness of bone marrow mesenchymal stem cells (BMMSCs) is crucial for bone homeostasis and regeneration. However, in vitro expansion and bone diseases impair BMMSC stemness, limiting its functionality in bone tissue engineering. Using a deep learning-based efficacy prediction system and bone tissue sequencing, we identify a natural small-molecule compound, dihydroartemisinin (DHA), that maintains BMMSC stemness and enhances bone regeneration. During long-term in vitro expansion, DHA preserves BMMSC stemness characteristics, including its self-renewal ability and unbiased differentiation. In an osteoporosis mouse model, oral administration of DHA restores the femur trabecular structure, bone density, and BMMSC stemness in situ. Mechanistically, DHA maintains BMMSC stemness by promoting histone 3 lysine 9 acetylation via GCN5 activation both in vivo and in vitro. Furthermore, the bone-targeted delivery of DHA by mesoporous silica nanoparticles improves its therapeutic efficacy in osteoporosis. Collectively, DHA could be a promising therapeutic agent for treating osteoporosis by maintaining BMMSC stemness.

Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration by rejuvenating senescent tendon stem/progenitor cells.

Adult tendon stem/progenitor cells (TSPCs) are essential for tendon maintenance, regeneration, and repair, yet they become susceptible to senescence with age, impairing the self-healing capacity of tendons. In this study, we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness. The top-ranked candidate, prim-O-glucosylcimifugin (POG), a saposhnikovia root extract, could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans, as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs. In vivo, the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals. Mechanistically, POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy. Thus, the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.