Dynamic regulation of innate lymphoid cell development during ontogeny.

The helper-like ILC contains various functional subsets, such as ILC1, ILC2, ILC3 and LTi cells, mediating the immune responses against viruses, parasites, and extracellular bacteria, respectively. Among them, LTi cells are also crucial for the formation of peripheral lymphoid tissues, such as lymph nodes. Our research, along with others', indicates a high proportion of LTi cells in the fetal ILC pool, which significantly decreases after birth. Conversely, the proportion of non-LTi ILCs increases postnatally, corresponding to the need for LTi cells to mediate lymphoid tissue formation during fetal stages and other ILC subsets to combat diverse pathogen infections postnatally. However, the regulatory mechanism for this transition remains unclear. In this study, we observed a preference for fetal ILC progenitors to differentiate into LTi cells, while postnatal bone marrow ILC progenitors preferentially differentiate into non-LTi ILCs. Particularly, this differentiation shift occurs within the first week after birth in mice. Further analysis revealed that adult ILC progenitors exhibit stronger activation of the Notch signaling pathway compared to fetal counterparts, accompanied by elevated Gata3 expression and decreased Rorc expression, leading to a transition from fetal LTi cell-dominant states to adult non-LTi ILC-dominant states. This study suggests that the body can regulate ILC development by modulating the activation level of the Notch signaling pathway, thereby acquiring different ILC subsets to accommodate the varying demands within the body at different developmental stages.

Improving anti-oxidant stress treatment of subarachnoid hemorrhage through self-assembled nanoparticles of oleanolic acid.

Subarachnoid hemorrhage (SAH) is a life-threatening acute hemorrhagic cerebrovascular disease, with early brain injury (EBI) being the main cause of high mortality and severe neurological dysfunction. Oxidative stress plays a crucial role in the pathogenesis of EBI. In this study, we synthesized antioxidant stress nanoparticles based on self-assembled oleanolic acid (OA) using the solvent volatilization method. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) techniques were employed to analyze and understand the self-assembly mechanism of oleic acid nanoparticles (OA NPs). The TUNEL assay, Nissl staining, and brain water content measurements were conducted to investigate the impact of OA NPs on cortical neuronal injury. Additionally, Western blot analysis was performed to investigate the antioxidant stress mechanism of OA NPs. The result showed that OA NPs exhibited a spherical structure with an average diameter of 168 nm. The application of OA NPs in SAH has been found to contribute to the reduction of keap1 protein levels and an increase in the nuclear level of Nrf2. As a result, the transcription of antioxidant stress proteins, including HO1 and NQO1, is triggered. The activation of the antioxidant stress pathway by OA NPs ultimately leads to a decrease in neuron damage and an improvement in neurological dysfunction. In conclusion, we successfully designed and synthesized OA NPs that can efficiently target the site of SAH. These nanoparticles have demonstrated their potential as antioxidants for the treatment of SAH, offering significant clinical applications.

Cucumber pathogenic spores' detection using the GCS-YOLOv8 network with microscopic images in natural scenes.

Fungal diseases are the main factors affecting the quality and production of vegetables. Rapid and accurate detection of pathogenic spores is of great practical significance for early prediction and prevention of diseases. However, there are some problems with microscopic images collected in the natural environment, such as complex backgrounds, more disturbing materials, small size of spores, and various forms. Therefore, this study proposed an improved detection method of GCS-YOLOv8 (Global context and CARFAE and Small detector-optimized YOLOv8), effectively improving the detection accuracy of small-target pathogen spores in natural scenes. Firstly, by adding a small target detection layer in the network, the network's sensitivity to small targets is enhanced, and the problem of low detection accuracy of the small target is effectively improved. Secondly, Global Context attention is introduced in Backbone to optimize the CSPDarknet53 to 2-Stage FPN (C2F) module and model global context information. At the same time, the feature up-sampling module Content-Aware Reassembly of Features (CARAFE) was introduced into Neck to enhance the ability of the network to extract spore features in natural scenes further. Finally, we used an Explainable Artificial Intelligence (XAI) approach to interpret the model's predictions. The experimental results showed that the improved GCS-YOLOv8 model could detect the spores of the three fungi with an accuracy of 0.926 and a model size of 22.8 MB, which was significantly superior to the existing model and showed good robustness under different brightness conditions. The test on the microscopic images of the infection structure of cucumber down mildew also proved that the model had good generalization. Therefore, this study realized the accurate detection of pathogen spores in natural scenes and provided feasible technical support for early predicting and preventing fungal diseases.

PD-L1 and B7-H3 are Effective Prognostic Factors and Potential Therapeutic Targets for High-Risk Thyroid Cancer.

The prognosis of thyroid cancer in patients varies significantly based on different pathological types or distinct clinical situations. Investigating the expression of immune checkpoint molecules PD-L1 and B7-H3 in high-risk thyroid cancer and their correlation with clinicopathological features and prognosis will contribute to the development of novel therapeutic strategies. A retrospective sample of 202 patients with thyroid cancer who underwent surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences was collected, including 33 cases of anaplastic thyroid cancer (ATC), 21 cases of differentiated thyroid cancer (DTC) with distant metastasis (DM), 7 cases of differentiated high-grade thyroid carcinoma (DHGTC), and 109 cases of aggressive subtypes of papillary thyroid carcinoma (PTC) (including 28 cases of tall cell PTC, 31 cases of diffuse sclerosing PTC, 20 cases of solid PTC, 15 cases of columnar cell PTC, and 15 cases of hobnail PTC). In the control group, there were 32 cases of classic PTC. The differences in protein expression between PD-L1 and B7-H3 in several high-risk thyroid cancers and normal tissues and controls were compared by immunohistochemical staining, and the clinicopathological features and prognostic relevance were statistically analyzed. The expression of PD-L1 in ATC (P < 0.001), tall cell PTC (P = 0.031), and DHGTC (P = 0.003) was significantly higher than that in classic PTC. The expression of B7-H3 in ATC (P < 0.001), DTC with DM (P = 0.001), diffuse sclerosing PTC (P = 0.013), columnar cell PTC (P = 0.007), solid PTC (P < 0.001), hobnail PTC (P < 0.001), and DHGTC (P < 0.001) was significantly higher than that in classic PTC. In ATC, PD-L1 expression correlated significantly with extrathyroidal extension (ETE) (P = 0.027) and B7-H3 expression correlated significantly with male patients (P = 0.031) and lymph node metastasis (LNM) (P = 0.026). The positive expression of B7-H3 (P = 0.041) was an independent risk factor for disease progression in ATC. B7-H3 positive expression (P = 0.049), PD-L1 positive expression (P = 0.015), and tumor diameter ≥ 2 cm (P = 0.038) were independent risk factors for disease progression in patients with DTC with DM. PD-L1 positive expression (P = 0.019) and tumor diameter ≥ 2 cm (P = 0.018) were independent risk factors for disease progression in patients with aggressive subtypes of PTC. B7-H3 and PD-L1 are expected to be effective prognostic indicators for patients with aggressive thyroid cancer, which can help in optimization of individualized treatment strategies. Immunotherapy targeting these two molecules may provide new and complementary ideas for the treatment of high-risk/refractory thyroid cancer.

Cephalopods' Skin-Inspired Design of Nanoscale Electronic Transport Layers for Adaptive Electrochromic Tuning.

Cephalopods can change their skin color by using high-speed electron transduction among receptors, neural networks, and pigmentary effectors. However, it remains challenging to realize a neuroelectrical transmission system like that found in cephalopods, where electrons/ions transmit on nanoscale, which is crucial for fast adaptive electrochromic tuning. Inspired by that, hereby an ideal, rapidly responsive, and multicolor electrochromic biomimetic skin is introduced. Specifically, the biomimetic skin comprises W18O49 nanowires (NWs) that are either colorless or blue, Au nanoparticles@polyaniline (Au NPs@PANI) ranging from green to pink, and a flexible conductive substrate. As the applied voltage changes from 0.4 V to -0.7 V and back to 0 V, the color of the biomimetic skin transforms from green to blue and ultimately to pink. This color change is attributed to the electrically induced redox reaction of Au NPs@PANI and W18O49 NWs, triggered by the transfer of electrons and ions. Furthermore, the high versatility and adaptability of electrical stimulus enable the creation of a highly interactive electrochromic biomimetic skin system through the integration of sensitive acoustic sensors, providing a perfect environment-responsive platform. This work provides a biomimetic multicolor electrochromic skin that depends on electron/ion transfer on nanoscale, expands potential uses for camouflage skin.

ZnO nanoparticles encapsulated cellulose-lignin film for antibacterial and biodegradable food packaging.

Foodborne illness caused by consuming foods contaminated by pathogens remains threating to the public health. Despite considerable efforts of using renewable source materials, it is highly demanding to fabricate food packaging with multiple properties including eco-friendliness, bactericidal effect and biocompatibility. Here, sodium lignosulfonate (SL) and ZnO nanoparticles (ZnO NPs) were used as functional filler and structure components, respectively, on the cellulose nanofibers (CNFs)-based films, which endows the produced membrane (CNF/SL-ZnO) the UV-light blocking, antioxidant, and antimicrobial characteristics. Due to the interconnected polymeric structure, the prepared CNF/SL-ZnO films possessed considerable mechanical properties, thermal stability, and good moisture barrier capability. Moreover, the tested samples exhibited an improved shelf life in food packaging. Furthermore, metagenome analysis revealed superior biodegradability of obtained films with negligible side effect on the soil microenvironment. Therefore, the biocompatible, degradable, and antibacterial CNF/SL-ZnO film holds enormous potential for sustainable uses including food packaging.

Compound heterozygous variants in SLC45A1 might cause syndromic intellectual disability by localization failure and activity attenuation in cells.

Intellectual disability (ID) is a kind of nervous developmental disorder and affects more than 1% of people worldwide. SLC45A1 as a transmembrane protein is implicated in the regulation of glucose homoeostasis. Through trio-based exome sequencing, the missense mutations of SLC45A1 c.103G>A (p.V35M) and c.1211T>G (p.F404C) were identified in the proband with syndromic ID. The distribution, expression and activity of SLC45A1 wild-type (WT) and variants were assayed in transfected COS7 cells. In SLC45A1 variants, the hydrogen bonds surrounding the 35th and 404th amino acid were changed, location on the cytomembrane was failed, their activity to transport glucose was also significantly decreased to contrast with SLC45A1-WT. No difference was observed at the mRNA and protein level. In conclusion, the compound heterozygous variants of SLC45A1 might be the genetic etiology for syndromic ID. These novel mutations probably attenuated its activity to transport glucose by the alteration of tertiary structure and failure of intracellular location.

Effect of dexmedetomidine on somatosensory- and motor-evoked potentials in patients receiving craniotomy under propofol-sevoflurane combined anesthesia.

Introduction: Dexmedetomidine is often used as an adjunct to total intravenous anesthesia (TIVA) for procedures requiring intraoperative neurophysiologic monitoring (IONM). However, it has been reported that dexmedetomidine might mask the warning of a neurological deficit on intraoperative monitoring. Methods: We reviewed the intraoperative neurophysiological monitoring data of 47 patients who underwent surgery and IONM from March 2019 to March 2021 at the Department of Neurosurgery, Renmin Hospital of Wuhan University. Pre- and postoperative motor function scores were recorded and analyzed. Dexmedetomidine was administered intravenously at 0.5 µg/kg/h 40 min after anesthesia and discontinued after 1 h in the dexmedetomidine group. Results: We found that the amplitude of transcranial motor-evoked potentials (Tce-MEPs) was significantly lower in the dexmedetomidine group than in the negative control group (P < 0.0001). There was no statistically significant difference in the somatosensory-evoked potentials (SSEPs) amplitude or the Tce-MEPs or SSEPs latency. There was no significant decrease in postoperative motor function in the dexmedetomidine group compared with the preoperative group, suggesting that there is no evidence that dexmedetomidine affects patient prognosis. In addition, we noticed a synchronized bilateral decrease in the Tce-MEPs amplitude in the dexmedetomidine group and a mostly unilateral decrease on the side of the brain injury in the positive control group (P = 0.001). Discussion: Although dexmedetomidine does not affect the prognosis of patients undergoing craniotomy, the potential risks and benefits of applying it as an adjunctive medication during craniotomy should be carefully evaluated. When dexmedetomidine is administered, Tce-MEPs should be monitored. When a decrease in the Tce-MEPs amplitude is detected, the cause of the decrease in the MEPs amplitude can be indirectly determined by whether the decrease is bilateral.

Chemotactic recruitment of genetically engineered cell membrane-camouflaged metal-organic framework nanoparticles for ischemic osteonecrosis treatment.

Ischemic osteonecrosis, particularly glucocorticoid-induced osteonecrosis of the femoral head (GIONFH), is primarily due to the dysfunction of osteogenesis and angiogenesis. miRNA, as a therapeutic system with immense potential, plays a vital role in the treatment of various diseases. However, due to the unique microenvironmental structure of bone tissue, especially in the case of GIONFH, where there is a deficiency in the vascular system, it is challenging to effectively target and deliver to the ischemic osteonecrosis area. A drug delivery system assisted by genetically engineered cell membranes holds promise in addressing the challenge of targeted miRNA delivery. Herein, we leverage the potential of miR-21 in modulating osteogenesis and angiogenesis to design an innovative biomimetic nanoplatform system. First, we employed metal-organic frameworks (MOFs) as the core structure to load miR-21-m (miR-21-m@MOF). The nanoparticles were further coated with the membrane of bone marrow mesenchymal stem cells overexpressing CXCR4 (CM-miR-21-m@MOF), enhancing their ability to target ischemic bone areas via the CXCR4-SDF1 axis. These biomimetic nanocomposites possess both bone-targeting and ischemia-guiding capabilities, actively targeting GIONFH lesions to release miR-21-m into target cells, thereby silencing PTEN gene and activating the PI3K-AKT signaling pathway to regulate osteogenesis and angiogenesis. This innovative miRNA delivery system provides a promising therapeutic avenue for GIONFH and potentially other related ischemic bone diseases. STATEMENT OF SIGNIFICANCE.

Simultaneous reconstruction of 3D fluorescence distribution and object surface using structured light illumination and dual-camera detection.

Fluorescence molecular tomography (FMT) serves as a noninvasive modality for visualizing volumetric fluorescence distribution within biological tissues, thereby proving to be an invaluable imaging tool for preclinical animal studies. The conventional FMT relies upon a point-by-point raster scan strategy, enhancing the dataset for subsequent reconstruction but concurrently elongating the data acquisition process. The resultant diminished temporal resolution has persistently posed a bottleneck, constraining its utility in dynamic imaging studies. We introduce a novel system capable of simultaneous FMT and surface extraction, which is attributed to the implementation of a rapid line scanning approach and dual-camera detection. The system performance was characterized through phantom experiments, while the influence of scanning line density on reconstruction outcomes has been systematically investigated via both simulation and experiments. In a proof-of-concept study, our approach successfully captures a moving fluorescence bolus in three dimensions with an elevated frame rate of approximately 2.5 seconds per frame, employing an optimized scan interval of 5 mm. The notable enhancement in the spatio-temporal resolution of FMT holds the potential to broaden its applications in dynamic imaging tasks, such as surgical navigation.

Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single-Arm, Open-Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer's Disease.

INTRODUCTION: ALZ-801/valiltramiprosate is a small-molecule oral inhibitor of beta amyloid (Aß) aggregation and oligomer formation being studied in a phase 2 trial in APOE4 carriers with early Alzheimer's disease (AD) to evaluate treatment effects on fluid and imaging biomarkers and cognitive assessments. METHODS: The single-arm, open-label phase 2 trial was designed to evaluate the effects of the ALZ-801 265 mg tablet taken twice daily (after 2 weeks once daily) on plasma fluid AD biomarkers, hippocampal volume (HV), and cognition over 104 weeks in APOE4 carriers. The study enrolled subjects aged 50-80 years, with early AD [Mini-Mental State Examination (MMSE) ≥ 22, Clinical Dementia Rating-Global (CDR-G) 0.5 or 1], apolipoprotein E4 (APOE4) genotypes including APOE4/4 and APOE3/4 genotypes, and positive cerebrospinal fluid (CSF) AD biomarkers or prior amyloid scans. The primary outcome was plasma p-tau181, HV evaluated by magnetic resonance imaging (MRI) was the key secondary outcome, and plasma Aß42 and Aß40 were the secondary biomarker outcomes. The cognitive outcomes were the Rey Auditory Verbal Learning Test and the Digit Symbol Substitution Test. Safety and tolerability evaluations included treatment-emergent adverse events and amyloid-related imaging abnormalities (ARIA). The study was designed and powered to detect 15% reduction from baseline in plasma p-tau181 at the 104-week endpoint. A sample size of 80 subjects provided adequate power to detect this difference at a significance level of 0.05 using a two-sided paired t-test. RESULTS: The enrolled population of 84 subjects (31 homozygotes and 53 heterozygotes) was 52% females, mean age 69 years, MMSE 25.7 [70% mild cognitive impairment (MCI), 30% mild AD] with 55% on cholinesterase inhibitors. Plasma p-tau181 reduction from baseline was significant (31%, p = 0.045) at 104 weeks and all prior visits; HV atrophy was significantly reduced (p = 0.0014) compared with matched external controls from an observational Early AD study. Memory scores showed minimal decline from baseline over 104 weeks and correlated significantly with decreased HV atrophy (Spearman's 0.44, p = 0.002). Common adverse events were COVID infection and mild nausea, and no drug-related serious adverse events were reported. Of 14 early terminations, 6 were due to nonserious treatment-emergent adverse events and 1 death due to COVID. There was no vasogenic brain edema observed on MRI over 104 weeks. CONCLUSIONS: The effect of ALZ-801 on reducing plasma p-tau181 over 2 years demonstrates target engagement and supports its anti-Aß oligomer action that leads to a robust decrease in amyloid-induced brain neurodegeneration. The significant correlation between reduced HV atrophy and cognitive stability over 2 years suggests a disease-modifying effect of ALZ-801 treatment in patients with early AD. Together with the favorable safety profile with no events of vasogenic brain edema, these results support further evaluation of ALZ-801 in a broader population of APOE4 carriers, who represent two-thirds of patients with AD. TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04693520 .

Modal Parameter Recursive Estimation of Concrete Arch Dams under Seismic Loading Using an Adaptive Recursive Subspace Method.

Modal parameter estimation is crucial in vibration-based damage detection and deserves increased attention and investigation. Concrete arch dams are prone to damage during severe seismic events, leading to alterations in their structural dynamic characteristics and modal parameters, which exhibit specific time-varying properties. This highlights the significance of investigating the evolution of their modal parameters and ensuring their accurate identification. To effectively accomplish the recursive estimation of modal parameters for arch dams, an adaptive recursive subspace (ARS) method with variable forgetting factors was proposed in this study. In the ARS method, the variable forgetting factors were adaptively updated by assessing the change rate of the spatial Euclidean distance of adjacent modal frequency identification values. A numerical simulation of a concrete arch dam under seismic loading was conducted by using ABAQUS software, in which a concrete damaged plasticity (CDP) model was used to simulate the dam body's constitutive relation, allowing for the assessment of damage development under seismic loading. Utilizing the dynamic responses obtained from the numerical simulation, the ARS method was implemented for the modal parameter recursive estimation of the arch dam. The identification results revealed a decreasing trend in the frequencies of the four initial modes of the arch dam: from an undamaged state characterized by frequencies of 0.910, 1.166, 1.871, and 2.161 Hz to values of 0.895, 1.134, 1.842, and 2.134 Hz, respectively. Concurrently, increases in the damping ratios of these modes were observed, transitioning from 4.44%, 4.28%, 5.42%, and 5.56% to 4.98%, 4.91%, 6.61%, and 6.85%%, respectively. The correlation of the identification results with damage progression validated the effectiveness of the ARS method. This study's outcomes have substantial theoretical and practical importance, facilitating the immediate comprehension of the dynamic characteristics and operational states of concrete arch dam structures.

The Effects of Simultaneous Aerobic Exercise and Video Game Training on Executive Functions and Brain Connectivity in Older Adults.

OBJECTIVE: The study was designed to examine the effects of simultaneous combination of aerobic exercise and video game training on executive functions (EFs) and brain functional connectivity in older adults. DESIGN: A four-armed, quasi-experimental study. SETTING AND PARTICIPANTS: Community-dwelling adults aged 55 years and older. METHODS: A total of 97 older adults were divided into one of four groups: aerobic exercise (AE), video game (VG), combined intervention (CI), and passive control (PC). Participants in intervention groups received 32 sessions of training over a 4-month period at a frequency of twice a week. EFs was evaluated using a composite score derived from a battery of neuropsychological tests. The Montreal Cognitive Assessment (MoCA) was employed to evaluate overall cognitive function, while the 6-Minute Walking Test (6MWT) was utilized to gauge physical function. Additionally, the functional connectivity (FC) of the frontal-parietal networks (FPN) was examined as a neural indicator of cognitive processing and connectivity changes. RESULTS: In terms of EFs, both VG and CI groups demonstrated improvement following the intervention. This improvement was particularly pronounced in the CI group, with a large effect size (Hedge's g = 0.83), while the VG group showed a medium effect size (Hedge's g = 0.56). A significant increase in MoCA scores was also observed in both the VG and CI groups, whereas a significant increase in 6MWT scores was observed in the AE and CI groups. Although there were no group-level changes observed in FC of the FPN, we found that changes in FC was behaviorally relevant as increased FC was associated with greater improvement in EFs. CONCLUSION: The study offers preliminary evidence that both video game training and combined intervention could enhance EFs in older adults. Simultaneous combined intervention may hold greater potential for facilitating EFs gains. The initial evidence for correlated changes in brain connectivity and EFs provides new insights into understanding the neural basis underlying the training gains.

TRIM33 plays a critical role in regulating dendritic cell differentiation and homeostasis by modulating Irf8 and Bcl2l11 transcription.

The development of distinct dendritic cell (DC) subsets, namely, plasmacytoid DCs (pDCs) and conventional DC subsets (cDC1s and cDC2s), is controlled by specific transcription factors. IRF8 is essential for the fate specification of cDC1s. However, how the expression of Irf8 is regulated is not fully understood. In this study, we identified TRIM33 as a critical regulator of DC differentiation and maintenance. TRIM33 deletion in Trim33fl/fl Cre-ERT2 mice significantly impaired DC differentiation from hematopoietic progenitors at different developmental stages. TRIM33 deficiency downregulated the expression of multiple genes associated with DC differentiation in these progenitors. TRIM33 promoted the transcription of Irf8 to facilitate the differentiation of cDC1s by maintaining adequate CDK9 and Ser2 phosphorylated RNA polymerase II (S2 Pol II) levels at Irf8 gene sites. Moreover, TRIM33 prevented the apoptosis of DCs and progenitors by directly suppressing the PU.1-mediated transcription of Bcl2l11, thereby maintaining DC homeostasis. Taken together, our findings identified TRIM33 as a novel and crucial regulator of DC differentiation and maintenance through the modulation of Irf8 and Bcl2l11 expression. The finding that TRIM33 functions as a critical regulator of both DC differentiation and survival provides potential benefits for devising DC-based immune interventions and therapies.

Bufotalin enhances apoptosis and TMZ chemosensitivity of glioblastoma cells by promoting mitochondrial dysfunction via AKT signaling pathway.

Glioblastoma multiforme (GBM) is the most prevalent and lethal primary intracranial neoplasm in the adult population, with treatments of limited efficacy. Recently, bufotalin has been shown to have anti-cancer activity in a variety of cancers. This investigation aims to investigate the effect of bufotalin on GBM and elucidate its potential underlying mechanism. Our results show that bufotalin not only inhibits the proliferation and epithelial-mesenchymal transition (EMT) but also triggers apoptosis in GBM cells. The result of RNA-seq indicated that bufotalin could induce mitochondrial dysfunction. Moreover, our observations indicate that bufotalin induces an excessive accumulation of intracellular reactive oxygen species (ROS) in GBM cells, leading to mitochondrial dysfunction and the dephosphorylation of AKT. Moreover, bufotalin improved TMZ sensitivity of GBM cells in vitro and in vivo. In conclusion, bufotalin enhances apoptosis and TMZ chemosensitivity of glioblastoma cells by promoting mitochondrial dysfunction via AKT signaling pathway.

Associations of Combined Exposure to Metabolic and Inflammatory Indicators with Thyroid Nodules in Adults: A Nested Case-Control Study.

Objective: To explore associations of combined exposure to metabolic/inflammatory indicators with thyroid nodules. Methods: We reviewed personal data for health screenings from 2020 to 2021. A propensity score matching method was used to match 931 adults recently diagnosed with thyroid nodules in a 1 : 4 ratio based on age and gender. Conditional logistic regression and Bayesian kernel machine regression (BKMR) were used to explore the associations of single metabolic/inflammatory indicators and the mixture with thyroid nodules, respectively. Results: In the adjusted models, five indicators (ORQ4 vs. Q1: 1.30, 95% CI: 1.07-1.58 for fasting blood glucose; ORQ4 vs. Q1: 1.30, 95% CI: 1.08-1.57 for systolic blood pressure; ORQ4 vs. Q1: 1.26, 95% CI: 1.04-1.53 for diastolic blood pressure; ORQ4 vs. Q1: 1.23, 95% CI: 1.02-1.48 for white blood cell; ORQ4 vs. Q1: 1.28, 95% CI: 1.07-1.55 for neutrophil) were positively associated with the risk of thyroid nodules, while high-density lipoproteins (ORQ3 vs. Q1: 0.75, 95% CI: 0.61-0.91) were negatively associated with the risk of thyroid nodules. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the metabolic and inflammatory mixture exhibited a significant positive association with thyroid nodules in a dose-response pattern, with systolic blood pressure being the greatest contributor within the mixture (conditional posterior inclusion probability of 0.82). No interaction effects were found among the five indicators. These associations were more prominent in males, participants with higher age (≥40 years old), and individuals with abnormal body mass index status. Conclusions: Levels of the metabolic and inflammatory mixture have a linear dose-response relationship with the risk of developing thyroid nodules, with systolic blood pressure levels being the most important contributor.

A tough, reversible and highly sensitive humidity actuator based on cellulose nanofiber films by intercalation modulated plasticization.

Cellulose nanofiber was an ideal candidate for humidity actuators based on its wide availability, biocompatibility and excellent hydrophilicity. However, conventional cellulose nanofiber-based actuators faced challenges like poor water resistance, flexibility, and sensitivity. Herein, water-resistant, flexible, and highly sensitive cross-linked cellulose nanofibers (CCNF) single-layer humidity actuators with remarkable reversible humidity responsiveness were prepared by combining the green click chemistry modification and intercalation modulated plasticization (IMP). The incorporation of phenyl ring and the crosslinked network structure in CCNF films contributed to its improved water resistance and mechanical properties (with a stress increased from 85.9 ± 3.1 MPa to 141.2 ± 21.5 MPa). SEM analysis confirmed enhanced interlaminar sliding properties facilitated by IMP. This resulted in increased flexibility and toughness of CCNF films, with a strain of 11.5 % and toughness of 9.9 MJ/m3. These improvements efficiently enhanced humidity sensitivity for cellulose nanofiber, with a 4.8-fold increase in bending curvature and a response time of only 3.4 ± 0.1 s. Finally, the good humidity sensitivity of modified CNF can be easily imparted to carbon nanotubes (CNTs) via simple self-assembly method, thus leading to a high-performance humidity-responsive actuator. The click chemistry modification and IMP offer a new avenue to fabricate tough, reversible and highly sensitive humidity actuator based on cellulose nanofiber.

Use of circulating tumor cells and microemboli to predict diagnosis and prognosis in diffuse glioma.

OBJECTIVE: Circulating tumor cell (CTC) detection is a promising noninvasive technique that can be used to diagnose cancer, monitor progression, and predict prognosis. In this study, the authors aimed to investigate the clinical utility of CTCs in the management of diffuse glioma. METHODS: Sixty-three patients with newly diagnosed diffuse glioma were included in this multicenter clinical cohort. The authors used a platform based on isolation by size of epithelial tumor cells (ISET) to detect and analyze CTCs and circulating tumor microemboli (CTMs) in the peripheral blood of patients both before and after surgery. Least absolute shrinkage and selector operation (LASSO) and Cox regression analyses were used to verify whether CTCs and CTMs are independent prognostic factors for diffuse glioma. RESULTS: CTC levels were closely related to the degree of malignancy, WHO grade, and pathological subtypes. Receiver operating characteristic curve analysis revealed that a high CTC level was a predictor for glioblastoma. The results also showed that CTMs originate from the parental tumor rather than from the circulation and are an independent prognostic factor for diffuse glioma. The postoperative CTC level is related to the peripheral immune system and patient survival. Cox regression analysis showed that postoperative CTC levels and CTM status are independent prognostic factors for diffuse glioma, and CTC- and CTM-based survival models had high accuracy in internal validation. CONCLUSIONS: The authors revealed a correlation between CTCs and clinical characteristics and demonstrated that CTCs and CTMs are independent predictors for the diagnosis and prognosis of diffuse glioma. Their CTC- and CTM-based survival models can enable clinicians to evaluate patients' response to surgery as well as their outcomes.

Novel potential lncRNA biomarker in B cells indicates essential pathogenic pathway activation in patients with SLE.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a highly heterogeneous disease, and B cell abnormalities play a central role in the pathogenesis of SLE. Long non-coding RNAs (lncRNAs) have also been implicated in the pathogenesis of SLE. The expression of lncRNAs is finely regulated and cell-type dependent, so we aimed to identify B cell-expressing lncRNAs as biomarkers for SLE, and to explore their ability to reflect the status of SLE critical pathway and disease activity. METHODS: Weighted gene coexpression network analysis (WGCNA) was used to cluster B cell-expressing genes of patients with SLE into different gene modules and relate them to clinical features. Based on the results of WGCNA, candidate lncRNA levels were further explored in public bulk and single-cell RNA-sequencing data. In another independent cohort, the levels of the candidate were detected by RT-qPCR and the correlation with disease activity was analysed. RESULTS: WGCNA analysis revealed one gene module significantly correlated with clinical features, which was enriched in type I interferon (IFN) pathway. Among non-coding genes in this module, lncRNA RP11-273G15.2 was differentially expressed in all five subsets of B cells from patients with SLE compared with healthy controls and other autoimmune diseases. RT-qPCR validated that RP11-273G15.2 was highly expressed in SLE B cells and positively correlated with IFN scores (r=0.7329, p<0.0001) and disease activity (r=0.4710, p=0.0005). CONCLUSION: RP11-273G15.2 could act as a diagnostic and disease activity monitoring biomarker for SLE, which might have the potential to guide clinical management.