Activation of Piezo1 or TRPV2 channels inhibits human ureteral contractions via NO release from the mucosa.

We aimed to investigate the expression and motor modulatory roles of several mechano-sensitive channels (MSCs) in human ureter. Human proximal ureters were obtained from eighty patients subjected to nephrectomy. Expression of MSCs at mRNA, protein and functional levels were examined. Contractions of longitudinal ureter strips were recorded in organ bath. A fluorescent probe Diaminofluoresceins was used to measure nitric oxide (NO). RT-PCR analyses revealed predominant expression of Piezo1 and TRPV2 mRNA in intact ureter and mucosa. Immunofluorescence assays indicate proteins of MSCs (Piezo1/Piezo2, TRPV2 and TRPV4) were mainly distributed in the urothelium. Ca2+ imaging confirmed functional expression of TRPV2, TRPV4 and Piezo1 in cultured urothelial cells. Specific agonists of Piezo1 (Yoda1, 3-300 µM) and TRPV2 (cannabidiol, 3-300 µM) attenuated the frequency of ureteral contractions in a dose-dependent manner while the TRPV4 agonist GSK1016790A (100 nM-1 µM) exerted no effect. The inhibitory effects of Piezo1 and TRPV2 agonists were significantly blocked by the selective antagonists (Dooku 1 for Piezo1, Tranilast for TRPV2), removal of the mucosa, and pretreatment with NO synthase inhibitor L-NAME (10 µM). Yoda1 (30 µM) and cannabidiol (50 µM) increased production of NO in cultured urothelial cells. Our results suggest that activation of Piezo1 or TRPV2 evokes NO production and release from mucosa that may mediate mechanical stimulus-induced reduction of ureter contractions. Our findings support the idea that targeting Piezo1 and TRPV2 channels may be a promising pharmacological strategy for ureter stone passage or colic pain relief.

Emerging probing perspective of two-dimensional materials physics: terahertz emission spectroscopy.

Terahertz (THz) emission spectroscopy (TES) has emerged as a highly effective and versatile technique for investigating the photoelectric properties of diverse materials and nonlinear physical processes in the past few decades. Concurrently, research on two-dimensional (2D) materials has experienced substantial growth due to their atomically thin structures, exceptional mechanical and optoelectronic properties, and the potential for applications in flexible electronics, sensing, and nanoelectronics. Specifically, these materials offer advantages such as tunable bandgap, high carrier mobility, wideband optical absorption, and relatively short carrier lifetime. By applying TES to investigate the 2D materials, their interfaces and heterostructures, rich information about the interplay among photons, charges, phonons and spins can be unfolded, which provides fundamental understanding for future applications. Thus it is timely to review the nonlinear processes underlying THz emission in 2D materials including optical rectification, photon-drag, high-order harmonic generation and spin-to-charge conversion, showcasing the rich diversity of the TES employed to unravel the complex nature of these materials. Typical applications based on THz emissions, such as THz lasers, ultrafast imaging and biosensors, are also discussed. Step further, we analyzed the unique advantages of spintronic terahertz emitters and the future technological advancements in the development of new THz generation mechanisms leading to advanced THz sources characterized by wide bandwidth, high power and integration, suitable for industrial and commercial applications. The continuous advancement and integration of TES with the study of 2D materials and heterostructures promise to revolutionize research in different areas, including basic materials physics, novel optoelectronic devices, and chips for post-Moore's era.

Research progress in the treatment of an immune system disease-type 1 diabetes-by regulating the intestinal flora with Chinese medicine and food homologous drugs.

Type 1 diabetes (T1D) is a specific autoimmune disease related to genetic and autoimmune factors. Recent studies have found that the intestinal flora is one of the important environmental factors in the development of T1D. The gut microbiota is the largest microbiota in the human body and has a significant impact on material and energy metabolism. Related studies have found that the intestinal floras of T1D patients are unbalanced. Compared with normal patients, the abundance of beneficial bacteria is reduced, and various pathogenic bacteria are significantly increased, affecting the occurrence and development of diabetes. Medicinal and food homologous traditional Chinese medicine (TCM) has a multicomponent, multitarget, and biphasic regulatory effect. Its chemical composition can increase the abundance of beneficial bacteria, improve the diversity of the intestinal flora, reduce blood sugar, and achieve the purpose of preventing and treating T1D by regulating the intestinal flora and its metabolites. Therefore, based on a review of T1D, intestinal flora, and TCM derived from medicine and food, this review describes the relationship between T1D and the intestinal flora, as well as the research progress of TCM interventions for T1D through regulation of the intestinal flora. Medicine and food homologous TCM has certain advantages in treating diabetes and regulating the intestinal flora. It can be seen that there is still great research space and broad development prospects for the treatment of diabetes by regulating the intestinal flora with drug and food homologous TCM.

Effect of pectin structure on the in vitro bioaccessibility of carotenoids in simulated juice model.

The impact of pectin structure on carotenoid bioaccessibility is still uncertain. This study aims to investigate how the different pectic polymers affected the bioaccessibility of carotenoids in a simulated juice model during static in vitro digestion. This study includes homogalacturonan (HG), which is a linear pectic polymer, rhamnogalacturonan-I (RG-I), which is a branched pectic polymer, and rhamnogalacturonan (RG), which is a diverse pectic polymer rich in RG-I, rhamnogalacturonan-II (RG-II), and xylogalacturonan domains. Juice models without pectin had the highest carotenoid bioaccessibility, suggesting pectin has negative effects on carotenoid bioaccessibility. During the intestinal phase, systems with HG showed the highest viscosity, followed by systems with RG and systems with RG-I. Systems with RG-I had lower carotenoid bioaccessibility than systems with HG and RG-II. Both the percentage of RG-I and the average side chain length of RG-I had negative correlations with carotenoid bioaccessibility. RG-I side chains with more arabinose and/or galactose might cause lower carotenoid bioaccessibility in this juice model system. This study offers valuable insights into the relationship between pectin structure and carotenoid bioaccessibility in a simulated juice model, highlighting the importance of considering pectin composition for maximizing carotenoid bioaccessibility and potential health benefits in fruit-based beverages.

Multiphase enhanced CT-based transformer for differential diagnosis and predicting surgical risk events of solid abdominal tumors in children.

BACKGROUND: For pediatric patients with solid abdominal tumors, early diagnosis can guide clinical treatment decisions, and comprehensive preoperative evaluation is essential to reduce surgical risk. The aim of this study was to explore the feasibility of multiphase enhanced CT-based transformer in the early diagnosis of tumors and prediction of surgical risk events (SRE). METHODS: A total of 496 pediatric patients with solid abdominal tumors were enrolled in the study. With Swin transformer, we constructed and trained two Swin-T models based on preoperative multiphase enhanced CT for personalized prediction of tumor type and SRE status. Subsequently, we comprehensively evaluated the performance of each model and constructed four benchmark models for performance comparison. RESULTS: There was no significant difference in SRE status between tumor types. In the diagnostic task, areas under the receiver operating characteristic curves (AUC) of the Swin-T model were 0.987 (95 % CI, 0.973-0.997) and 0.844 (95 % CI, 0.730-0.940) in the training and validation cohorts, respectively. In predicting SRE, AUCs of the Swin-T model were 0.920 (95 % CI, 0.885-0.948) and 0.741 (95 % CI, 0.632-0.838) in the training and test cohorts, respectively. The Swin-T model achieved the best performance in both classification tasks compared to benchmark models. CONCLUSION: The Swin-T model is a promising tool to assist pediatricians in the differential diagnosis of abdominal tumors and in comprehensive preoperative evaluation.

Design of a dual hollow beam optical antenna based on a Fresnel lens-conical lens combination.

To improve the transmission efficiency of Cassegrain antennas and enable the simultaneous transmission of signals with different wavelengths in the antenna system, this study introduces Fresnel lenses and conical lenses in front of the Cassegrain antenna at the transmitting end. Reflective mirrors and focusing lenses are introduced at the receiving end. A detailed description is provided of the design process for the Fresnel lens, as well as the impact of various parameters on the hollow radius when combined with the conical lens. Based on the laws of vector reflection and refraction, simulations are performed to track the propagation of light through the entire communication system and lens pairs, providing transmission efficiency plots of the antenna system under deflection and off-axis conditions. Taking into account practical factors such as lens chamfer, transmittance, Cassegrain antenna reflectance, and material dispersion, the transmission efficiency of the antenna system at 1550 nm wavelength can still reach 93.45%. The proposed method not only improves the transmission efficiency of Cassegrain antennas, but also enables the transmission of different information through the inner and outer layers of the antenna system.

Engineered Niobium Carbide MXenzyme-Integrated Self-Adaptive Coatings Inhibiting Periprosthetic Osteolysis by Orchestrating Osteogenesis-Osteoclastogenesis Balance.

Periprosthetic osteolysis induced by the ultrahigh-molecular-weight polyethylene (UHMWPE) wear particles is a major complication associated with the sustained service of artificial joint prostheses and often necessitates revision surgery. Therefore, a smart implant with direct prevention and repair abilities is urgently developed to avoid painful revision surgery. Herein, we fabricate a phosphatidylserine- and polyethylenimine-engineered niobium carbide (Nb2C) MXenzyme-coated micro/nanostructured titanium implant (PPN@MNTi) that inhibits UHMWPE particle-induced periprosthetic osteolysis. The specific mechanism by which PPN@MNTi operates involves the bioresponsive release of nanosheets from the MNTi substrate within an osteolysis microenvironment, initiated by the cleavage of a thioketal-dopamine molecule sensitive to reactive oxygen species (ROS). Subsequently, functionalized Nb2C MXenzyme could target macrophages and escape from lysosomes, effectively scavenging intracellular ROS through its antioxidant nanozyme-mimicking activities. This further achieves the suppression of osteoclastogenesis by inhibiting NF-κB/MAPK and autophagy signaling pathways. Simultaneously, based on the synergistic effect of MXenzyme-integrated coatings and micro/nanostructured topography, the designed implant promotes the osteogenic differentiation of bone mesenchymal stem cells to regulate bone homeostasis, further achieving advanced osseointegration and alleviable periprosthetic osteolysis in vivo. This study provides a precise prevention and repair strategy of periprosthetic osteolysis, offering a paradigm for the development of smart orthopedic implants.

Overtone photothermal microscopy for high-resolution and high-sensitivity vibrational imaging.

Photothermal microscopy is a highly sensitive pump-probe method for mapping nanostructures and molecules through the detection of local thermal gradients. While visible photothermal microscopy and mid-infrared photothermal microscopy techniques have been developed, they possess inherent limitations. These techniques either lack chemical specificity or encounter significant light attenuation caused by water absorption. Here, we present an overtone photothermal (OPT) microscopy technique that offers high chemical specificity, detection sensitivity, and spatial resolution by employing a visible probe for local heat detection in the C-H overtone region. We demonstrate its capability for high-fidelity chemical imaging of polymer nanostructures, depth-resolved intracellular chemical mapping of cancer cells, and imaging of multicellular C. elegans organisms and highly scattering brain tissues. By bridging the gap between visible and mid-infrared photothermal microscopy, OPT establishes a new modality for high-resolution and high-sensitivity chemical imaging. This advancement complements large-scale shortwave infrared imaging approaches, facilitating multiscale structural and chemical investigations of materials and biological metabolism.

Effects of chronic aerobic exercise on attentional bias among women with methamphetamine addiction.

Objective: To explore the effects of chronic exercise on attentional bias toward drug-related stimuli and on brain electrophysiological characteristics among women with methamphetamine addiction. Methods: In total, 63 women with methamphetamine addiction were randomized to participate in a dance (n = 21; mean age, 32.16 ± 2.07 years), bicycle (n = 21; mean age, 32.59 ± 2.12 years), or control (maintained regular activities with little exercise; n = 21; mean age, 30.95 ± 2.81 years) group for 12 weeks. The participants in the three groups were not significantly different in terms of methamphetamine use or detoxification. Before and after the intervention, attentional bias was assessed using the dot-probe task, and event-related potentials were recorded during the task. Results: The mean attentional bias scores decreased significantly after the intervention in both exercise groups but not in the control group. After 12 weeks of dance exercise, the amplitudes of the N170, N2, P2, and P3 components of the event-related potentials decreased significantly during attentional bias processing. In addition, differences in N170 amplitudes for congruent vs. incongruent conditions in the dot-probe task were no longer observed. After 12 weeks of cycling exercise, N2 and P2 amplitudes decreased significantly. By contrast, there were no significant differences in N170, N2, P2, and P3 amplitudes in the control group before vs. after the intervention. Conclusions: Chronic (12 weeks of) aerobic exercise reduced attentional bias toward drug-related cues by improving attentional inhibition and reducing the maintenance of extra attention to drug-related cues among women with methamphetamine addiction. Both dance and bicycle exercise improved the early recognition of drug-related cues, weakened the influence of the memory of previous drug use, and improved attentional bias behavior by strengthening attention control. Dance exercise, but not bicycling, also regulated emotional control and improved the attention selection process. These results provide theoretical and empirical evidence that chronic aerobic exercise may reduce the attentional bias toward drug-related cues to assist in the recovery of women with methamphetamine addiction.

Suppression of lysosome metabolism-meditated GARP/TGF-ß1 complexes specifically depletes regulatory T cells to inhibit breast cancer metastasis.

Regulatory T cells (Tregs) prevent autoimmunity and contribute to cancer progression. They exert contact-dependent inhibition of immune cells through the production of active transforming growth factor-ß1 (TGF-ß1). However, the absence of a specific surface marker makes inhibiting the production of active TGF-ß1 to specifically deplete human Tregs but not other cell types a challenge. TGF-ß1 in an inactive form binds to Tregs membrane protein Glycoprotein A Repetitions Predominant (GARP) and then activates it via an unknown mechanism. Here, we demonstrated that tumour necrosis factor receptor-associated factor 3 interacting protein 3 (TRAF3IP3) in the Treg lysosome is involved in this activation mechanism. Using a novel naphthalenelactam-platinum-based anticancer drug (NPt), we developed a new synergistic effect by suppressing ATP-binding cassette subfamily B member 9 (ABCB9) and TRAF3IP3-mediated divergent lysosomal metabolic programs in tumors and human Tregs to block the production of active GARP/TGF-ß1 for remodeling the tumor microenvironment. Mechanistically, NPt is stored in Treg lysosome to inhibit TRAF3IP3-meditated GARP/TGF-ß1 complex activation to specifically deplete Tregs. In addition, by promoting the expression of ABCB9 in lysosome membrane, NPt inhibits SARA/p-SMAD2/3 through CHRD-induced TGF-ß1 signaling pathway. In addition to expose a previously undefined divergent lysosomal metabolic program-meditated GARP/TGF-ß1 complex blockade by exploring the inherent metabolic plasticity, NPt may serve as a therapeutic tool to boost unrecognized Treg-based immune responses to infection or cancer via a mechanism distinct from traditional platinum drugs and currently available immune-modulatory antibodies.

Oral mitochondrial transplantation using nanomotors to treat ischaemic heart disease.

Mitochondrial transplantation is an important therapeutic strategy for restoring energy supply in patients with ischaemic heart disease (IHD); however, it is limited by the invasiveness of the transplantation method and loss of mitochondrial activity. Here we report successful mitochondrial transplantation by oral administration for IHD therapy. A nitric-oxide-releasing nanomotor is modified on the mitochondria surface to obtain nanomotorized mitochondria with chemotactic targeting ability towards damaged heart tissue due to nanomotor action. The nanomotorized mitochondria are packaged in enteric capsules to protect them from gastric acid erosion. After oral delivery the mitochondria are released in the intestine, where they are quickly absorbed by intestinal cells and secreted into the bloodstream, allowing delivery to the damaged heart tissue. The regulation of disease microenvironment by the nanomotorized mitochondria can not only achieve rapid uptake and high retention of mitochondria by damaged cardiomyocytes but also maintains high activity of the transplanted mitochondria. Furthermore, results from animal models of IHD indicate that the accumulated nanomotorized mitochondria in the damaged heart tissue can regulate cardiac metabolism at the transcriptional level, thus preventing IHD progression. This strategy has the potential to change the therapeutic strategy used to treat IHD.

Assessing the Risk of Bias in Randomized Clinical Trials With Large Language Models.

Importance: Large language models (LLMs) may facilitate the labor-intensive process of systematic reviews. However, the exact methods and reliability remain uncertain. Objective: To explore the feasibility and reliability of using LLMs to assess risk of bias (ROB) in randomized clinical trials (RCTs). Design, Setting, and Participants: A survey study was conducted between August 10, 2023, and October 30, 2023. Thirty RCTs were selected from published systematic reviews. Main Outcomes and Measures: A structured prompt was developed to guide ChatGPT (LLM 1) and Claude (LLM 2) in assessing the ROB in these RCTs using a modified version of the Cochrane ROB tool developed by the CLARITY group at McMaster University. Each RCT was assessed twice by both models, and the results were documented. The results were compared with an assessment by 3 experts, which was considered a criterion standard. Correct assessment rates, sensitivity, specificity, and F1 scores were calculated to reflect accuracy, both overall and for each domain of the Cochrane ROB tool; consistent assessment rates and Cohen κ were calculated to gauge consistency; and assessment time was calculated to measure efficiency. Performance between the 2 models was compared using risk differences. Results: Both models demonstrated high correct assessment rates. LLM 1 reached a mean correct assessment rate of 84.5% (95% CI, 81.5%-87.3%), and LLM 2 reached a significantly higher rate of 89.5% (95% CI, 87.0%-91.8%). The risk difference between the 2 models was 0.05 (95% CI, 0.01-0.09). In most domains, domain-specific correct rates were around 80% to 90%; however, sensitivity below 0.80 was observed in domains 1 (random sequence generation), 2 (allocation concealment), and 6 (other concerns). Domains 4 (missing outcome data), 5 (selective outcome reporting), and 6 had F1 scores below 0.50. The consistent rates between the 2 assessments were 84.0% for LLM 1 and 87.3% for LLM 2. LLM 1's κ exceeded 0.80 in 7 and LLM 2's in 8 domains. The mean (SD) time needed for assessment was 77 (16) seconds for LLM 1 and 53 (12) seconds for LLM 2. Conclusions: In this survey study of applying LLMs for ROB assessment, LLM 1 and LLM 2 demonstrated substantial accuracy and consistency in evaluating RCTs, suggesting their potential as supportive tools in systematic review processes.

Positive association of the anti-aging protein α-Klotho with insulin resistance and its inverse L-shaped relationship with glycaemic control in the middle-aged and elderly population.

PURPOSE: α-Klotho has been linked to insulin resistance (IR) in basic research. However, experimental evidence is inconsistent, and there is a lack of data from human research. This study seeks to elucidate the association of α-Klotho with IR in a nationwide, multiracial population. METHODS: A total of 5289 participants aged 40-79 years were included in the National Health and Nutrition Examination Survey (NHANES) spanning 2007-2016. Serum α-Klotho was measured using enzyme-linked immunosorbent assays (ELISA), and IR was evaluated by the homeostatic model assessment of insulin resistance (HOMA-IR). Weighted multivariate logistic and linear regression analysis, subgroup analysis stratified by demographic characteristics, medical condition or obesity status, and sensitivity analysis using propensity score matching (PSM) were performed. Restricted cubic splines (RCS) were performed to explore the nonlinear relationship. RESULTS: In the fully adjusted logistic regression model, a significant positive association was observed between log-transformed α-Klotho and IR (OR = 3.63, 95% CI: 1.56, 8.45), particularly in males or nonobese individuals (Pinteraction < 0.05). In the linear regression model, log10(α-Klotho) was associated with fasting blood glucose (FBG, ß = 1.25, 95% CI: 0.74, 1.76) and glycosylated hemoglobin (HbA1c, ß = 0.49, 95% CI: 0.20, 0.77). RCS revealed an inverse L-shaped dose-response relationship of α-Klotho with FBG and HbA1c (Pnonlinear <0.05). Beyond the inflection point of log10(α-Klotho) at 2.79, ß coefficients sharply rose for these glycaemic control indicators. CONCLUSION: The study provides clinical evidence supporting a positive association between α-Klotho and IR. Moreover, the inverse L-shaped relationship suggests that α-Klotho should reach a certain level to predict glycaemic changes effectively.

Microglial gp91phox-mediated neuroinflammation and ferroptosis contributes to learning and memory deficits in rotenone-treated mice.

Apart from dopaminergic neurotoxicity, exposure to rotenone, a commonly used insecticide in agriculture, also adversely affects hippocampal and cortical neurons, resulting in cognitive impairments in mice. We recently established a role of microglia-mediated neuroinflammation in rotenone-elicited deficits of cognition, yet the mechanisms remain elusive. Here, we investigated the involvement of NADPH oxidase 2 (NOX2) catalytic subunit gp91phox in rotenone-induced cognitive deficits and the associated mechanisms. Our study demonstrated that rotenone exposure elevated expression of gp91phox and phosphorylation of the NOX2 cytosolic subunit p47phox, along with NADPH depletion in the hippocampus and cortex of mice, indicating NOX2 activation. Specific knockdown of gp91phox in microglia via adeno-associated virus delivery resulted in reduced microglial activation, proinflammatory gene expression and improved learning and memory capacity in rotenone-intoxicated mice. Genetic deletion of gp91phox also reversed rotenone-elicited cognitive dysfunction in mice. Furthermore, microglial gp91phox knockdown attenuated neuronal damage and synaptic loss in mice. This intervention also suppressed iron accumulation, disruption of iron-metabolism proteins and iron-dependent lipid peroxidation and restored the balance of ferroptosis-related parameters, including GPX4, SLC711, PTGS2, and ACSL4 in rotenone-lesioned mice. Intriguingly, pharmacological inhibition of ferroptosis with liproxstatin-1 conferred protection against rotenone-induced neurodegeneration and cognitive dysfunction in mice. In summary, our findings underscored the contribution of microglial gp91phox-dependent neuroinflammation and ferroptosis to learning and memory dysfunction in rotenone-lesioned mice. These results provided valuable insights into the pathogenesis of cognitive deficits associated with pesticide-induced Parkinsonism, suggesting potential therapeutic avenues for intervention.

A Self-supervised Learning-Based Fine-Grained Classification Model for Distinguishing Malignant From Benign Subcentimeter Solid Pulmonary Nodules.

RATIONALE AND OBJECTIVES: Diagnosing subcentimeter solid pulmonary nodules (SSPNs) remains challenging in clinical practice. Deep learning may perform better than conventional methods in differentiating benign and malignant pulmonary nodules. This study aimed to develop and validate a model for differentiating malignant and benign SSPNs using CT images. MATERIALS AND METHODS: This retrospective study included consecutive patients with SSPNs detected between January 2015 and October 2021 as an internal dataset. Malignancy was confirmed pathologically; benignity was confirmed pathologically or via follow-up evaluations. The SSPNs were segmented manually. A self-supervision pre-training-based fine-grained network was developed for predicting SSPN malignancy. The pre-trained model was established using data from the National Lung Screening Trial, Lung Nodule Analysis 2016, and a database of 5478 pulmonary nodules from the previous study, with subsequent fine-tuning using the internal dataset. The model's efficacy was investigated using an external cohort from another center, and its accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined. RESULTS: Overall, 1276 patients (mean age, 56 ± 10 years; 497 males) with 1389 SSPNs (mean diameter, 7.5 ± 2.0 mm; 625 benign) were enrolled. The internal dataset was specifically enriched for malignancy. The model's performance in the internal testing set (316 SSPNs) was: AUC, 0.964 (95% confidence interval (95%CI): 0.942-0.986); accuracy, 0.934; sensitivity, 0.965; and specificity, 0.908. The model's performance in the external test set (202 SSPNs) was: AUC, 0.945 (95% CI: 0.910-0.979); accuracy, 0.911; sensitivity, 0.977; and specificity, 0.860. CONCLUSION: This deep learning model was robust and exhibited good performance in predicting the malignancy of SSPNs, which could help optimize patient management.

Research progress on the mechanism of TCM regulating intestinal microbiota in the treatment of DM mellitus.

In recent years, with the improvement of people's living standards, the incidence of DM has increased year by year in China. DM is a common metabolic syndrome characterized by hyperglycemia caused by genetic, environmental and other factors. At the same time, long-term suffering from DM will also have an impact on the heart, blood vessels, eyes, kidneys and nerves, and associated serious diseases. The human body has a large and complex gut microbiota, which has a significant impact on the body's metabolism. Research shows that the occurrence and development of DM and its complications are closely related to intestinal microbiota. At present, western medicine generally treats DM with drugs. The hypoglycemic effect is fast and strong, but it can have a series of side effects on the human body. Compared with western medicine, Chinese medicine has its unique views and methods in treating DM. TCM can improve symptoms and treat complications by improving the imbalance of microbiota in patients with DM. Its characteristics of health, safety, and reliability are widely accepted by the general public. This article reviews the relationship between intestinal microbiota and DM, as well as the mechanism of TCM intervention in DM by regulating intestinal microbiota.

Predicting epidermal growth factor receptor mutations in non-small cell lung cancer through dual-layer spectral CT: a prospective study.

OBJECTIVE: To determine whether quantitative parameters of detector-derived dual-layer spectral computed tomography (DLCT) can reliably identify epidermal growth factor receptor (EGFR) mutation status in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC who underwent arterial phase (AP) and venous phase (VP) DLCT between December 2021 and November 2022 were subdivided into the mutated and wild-type EGFR groups following EGFR mutation testing. Their baseline clinical data, conventional CT images, and spectral images were obtained. Iodine concentration (IC), iodine no water (INW), effective atomic number (Zeff), virtual monoenergetic images, the slope of the spectral attenuation curve (λHU), enhancement degree (ED), arterial enhancement fraction (AEF), and normalized AEF (NAEF) were measured for each lesion. RESULTS: Ninety-two patients (median age, 61 years, interquartile range [51, 67]; 33 men) were evaluated. The univariate analysis indicated that IC, normalized IC (NIC), INW and ED for the AP and VP, as well as Zeff and λHU for the VP were significantly associated with EGFR mutation status (all p < 0.05). INW(VP) showed the best diagnostic performance (AUC, 0.892 [95% confidence interval {CI}: 0.823, 0.960]). However, neither AEF (p = 0.156) nor NAEF (p = 0.567) showed significant differences between the two groups. The multivariate analysis showed that INW(AP) and NIC(VP) were significant predictors of EGFR mutation status, with the latter showing better performance (p = 0.029; AUC, 0.897 [95% CI: 0.816, 0.951] vs. 0.774 [95% CI: 0.675, 0.855]). CONCLUSION: Quantitative parameters of DLCT can help predict EGFR mutation status in patients with NSCLC. CRITICAL RELEVANCE STATEMENT: Quantitative parameters of DLCT, especially NIC(VP), can help predict EGFR mutation status in patients with NSCLC, facilitating appropriate and individualized treatment for them. KEY POINTS: Determining EGFR mutation status in patients with NSCLC before starting therapy is essential. Quantitative parameters of DLCT can predict EGFR mutation status in NSCLC patients. NIC in venous phase is an important parameter to guide individualized treatment selection for NSCLC patients.

Utilizing Joukowsky transformation in the design of optical fiber for elliptical-to-circular mode conversion.

This study addresses the challenge of enhancing coupling efficiency between optical fibers and elliptical Gaussian beams emitted by semiconductor lasers, particularly in fiber communication systems. We introduce a method for fiber design utilizing the Joukowsky transformation to facilitate efficient mode transformation from elliptical to circular, thereby augmenting the coupling efficiency with both single-mode and multimode fibers. Theoretical analysis and numerical simulations demonstrate that the fiber with a structurally transitional core maintains high-efficiency mode transformation across various lengths, and its structure has been optimized accordingly. Additionally, our investigation reveals the designed fiber's ability to preserve polarization states, which could have significant implications in precision optical applications. The proposed design offers an approach to improving performance in optical communication systems, especially in wavelength-division multiplexing (WDM) transmission systems and fiber lasers.

Manganese induces podocyte injury through regulating MTDH/ALKBH5/NLRP10 axis: Combined analysis at epidemiology and molecular biology levels.

Manganese (Mn) is an essential micronutrient required for various biological processes but excess exposure to Mn can cause neurotoxicity. However, there are few reports regarding the toxicity effect of Mn on the kidney as well as the underlying molecule mechanism. Herein, in vivo experiments were adopted to assess the toxicity effects associated with Mn, and found that chronic Mn treatment induced the injury of glomerular podocytes but not renal tubule in rats. Genome-wide CRISPR/Cas9 knockout screen was then employed to explore the biotargets of the toxic effect of Mn on podocytes. Through functional analyses of the enriched candidate genes, NLRP10 was found to be significantly up-regulated and mediated Mn-induced podocyte apoptosis. Further mechanism investigation revealed that NLRP10 expression was regulated by demethylase AlkB homolog 5 (ALKBH5) in an m6A-dependent fashion upon Mn treatment. Moreover, Mn could directly bind to Metadherin (MTDH) and promoted its combination with ALKBH5 to promote NLRP10 expression and cell apoptosis. Finally, logistic regressions, restricted cubic spline regressions and uniform cubic B-spline were used to investigate the association between Mn exposure and the risk of chronic kidney disease (CKD). A U-shaped nonlinear relationship between CKD risk and plasma Mn level, and a positive linear relationship between CKD risk and urinary Mn levels was found in our case-control study. To sum up, our findings illustrated that m6A-dependent NLRP10 regulation is indispensable for podocyte apoptosis and nephrotoxicity induced by Mn, providing fresh insight into understanding the health risk of Mn and a novel target for preventing renal injury in Mn-intoxicated patients.

Dish spliced concentrator with both uniform and focused performance through a variable focal length.

We present a dish spliced concentrator (DSC) featuring hexagonal spherical sub-mirrors of uniform size. The DSC offers advantages over traditional parabolic dish concentrators, including a compact layout, cost-effectiveness, higher concentration ratio, and improved light uniformity. Its versatility allows for both uniform and focused light concentration by adjusting parameters like the focal length of the DSC, making it suitable for concentrating photovoltaic (CPV) and concentrating solar thermal (CST) applications. We design the DSC using three-dimensional (3D) vector rotation theory, implementing ray tracing and transmission characteristic analysis based on three-dimensional vector reflection theory. We establish a simulation model to evaluate the impact of geometric parameters on the DSC's optical performance.