PAK3 Exacerbates Cardiac Lipotoxicity via SREBP1c in Obesity Cardiomyopathy.

Obesity-induced lipid overload in cardiomyocytes contributes to profound oxidative stress and cardiomyopathy, culminating in heart failure. In this study, we investigate a novel mechanism whereby lipids accumulate in cardiomyocytes and seek the relevant treatment strategies. P21-activated kinase 3 (PAK3) was elevated in obese human myocardium, and the murine hearts and cardiomyocytes upon diet- or fatty acid-induced stress, respectively. Mice with cardiac-specific overexpression of PAK3 were more susceptible to the development of cardiac dysfunction upon diet stress, at least partially, due to increased deposition of toxic lipids within the myocardium. Mechanistically, PAK3 promoted the nuclear expression of sterol regulatory element binding protein 1c (SREBP1c) through activation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase beta-1 (S6K1) pathway in cardiomyocytes, resulting in abnormal lipid genes profile, accumulation of excessive lipids, and oxidative stress. More importantly, PAK3 knockdown attenuated fatty acid-induced lipotoxicity and cell death in rat and human cardiomyocytes. More importantly, the S6K1 or SREBP1c inhibitor alleviated PAK3-triggered intracellular lipid overload and cardiac dysfunction under obese stress. Collectively, we have demonstrated that PAK3 impairs myocardial lipid homeostasis, while inhibition of cardiac lipotoxicity mitigates cardiac dysfunction. Our study provides a promising therapeutic strategy for ameliorating obesity cardiomyopathy.

Bu-Sui-Dan Enhances Osteoblast Differentiation by Upregulating VGLL4 to Counteract TEAD4-Mediated RUNX2 Transcription Suppression in Ovariectomized Rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Postmenopausal osteoporosis (PMOP) has been considered as a major causative factor for bone-joint pain and inducing pathologic fractures. Bu-Sui-Dan (BSD), a classic ancient herbal formula, has been shown to exhibit osteoprotective effects by promoting bone marrow development and bone growth. However, the exact mechanism of BSD are still unexplored. AIM OF STUDY: The study aimed to investigate the protective effect of BSD against osteoporotic injury, and to explore whether BSD regulated BMSCs' osteogenic differentiation by targeting VGLL4, which in turn improved PMOP. MATERIALS AND METHODS: The anti-osteoporotic effect of BSD was studied in ovariectomized (OVX) rats and bone marrow mesenchymal stem cells (BMSCs). Micro-CT imaging and HE staining were performed, and the levels of osteogenic protein RUNX2 and osteogenesis-related factor VGLL4 were determined. Co-immunoprecipitation (Co-IP) was further employed to delve into the effects of BSD on the interactions between TEAD4 and RUNX2. The key osteogenic factors 1ALP, COLl1A1, and Osterix expression were detected by RT-qPCR. Co-IP and proximity ligation assay (PLA) were employed to scrutinize the influence of BSD on TEAD4 and RUNX2 inter-binding. Moreover, VGLL4 knockdown in BMSCs was conducted to confirm the role of VGLL4 in the therapeutic mechanism of BSD. RESULTS: BSD showed a dose-dependent protective effect against osteoporotic injury, as evidenced by improvement in bone volume, bone microarchitecture, and histomorphometry. Additionally, BSD treatment increased the levels of RUNX2 and its downstream target genes including ALP, COL1A1, and Osterix. Moreover, BSD upregulated VGLL4 expression and lessened TEAD4-RUNX2 interactions. In BMSCs experiment, BSD-containing serum could promote osteogenic differentiation of BMSCs, boosted the expression of osteogenesis-related factors and VGLL4 level. The knockdown of VGLL4 in BMSCs diminished the promotion effect of BSD in osteoblast differentiation, suggesting that VGLL4 play a vital role in the therapeutic effects exerted by BSD. CONCLUSION: BSD ameliorated osteoporosis injury and promoted osteoblast differentiation through upregulation of VGLL4 levels, which in turn antagonized TEAD4-mediated RUNX2 transcriptional repression. Our study implied that BSD may be an osteoporosis therapeutic agent.

KIAA1199/CEMIP knockdown attenuates cardiac remodeling post myocardial infarction by activating TSP4 pathway in mice.

BACKGROUND: Excessive activation of cardiac fibroblasts (CFs) significantly contributes to adverse cardiac remodeling post-myocardial infarction (MI). CEMIP, initially recognized as an enzyme involved in hyaluronic acid (HA) degradation, has also been implicated in the activation of pulmonary fibroblasts. Nevertheless, the role and mechanism of CEMIP in adverse cardiac remodeling following MI remain largely unexplored. MATERIALS AND METHODS: RNA sequencing (RNA-seq) was performed on cardiac tissue harvested from the infarct/peri-infarct region of mice 28 days post-MI. RNA-seq was conducted on primary cardiac fibroblasts (CFs) transfected with adenovirus overexpressing CEMIP. Adeno-associated virus serotype 9 (AAV9) was engineered for in vivo CEMIP knockdown to elucidate its impact on cardiac remodeling. Immunoprecipitation coupled with mass spectrometry (IP-MS) and co-immunoprecipitation (co-IP) were employed to elucidate the mechanism by which CEMIP affected cardiac remodeling. KEY FINDINGS: RNA-seq of fibrotic heart tissue at day 28 post-MI revealed a significant upregulation of CEMIP. In vitro, CEMIP facilitated the activation of cardiac fibroblasts. In vivo, knockdown of CEMIP markedly reduced cardiac fibrosis and improved cardiac function post-MI. IP-MS and co-immunoprecipitation (co-IP) confirmed that CEMIP interacted with TSP4 through the G8 domain. Further experiments confirmed that CEMIP promoted TSP4 degradation in lysosomes in an ACTN4-dependent manner, thereby activating the FAK signaling pathway. SIGNIFICANCE: Our findings suggest that CEMIP significantly contributes to cardiac remodeling post-MI, which might be a novel approach for treating cardiac fibrosis following MI.

Investigating the Prognostic and Oncogenic Roles of Membrane-Associated Ring-CH-Type Finger 9 in Colorectal Cancer.

Backgroundsand Aims. Colorectal cancer (CRC) represents a major global health challenge, necessitating comprehensive investigations into its underlying molecular mechanisms to enhance diagnostic and therapeutic strategies. This study focuses on elucidating the oncogenic role of Membrane-Associated Ring-CH-Type Finger 9 (MARCHF9), a RING-Type E3 ubiquitin transferase, in CRC. We aim to assess MARCHF9's clinical significance, functional impact on CRC progression, and its potential as a prognostic biomarker. Methods. We leveraged data from the Cancer Genome Atlas (TCGA) cohort to evaluate MARCHF9 expression profiles in CRC. In vitro experiments involved siRNA-mediated MARCHF9 knockdown in COAD cell lines (SW480 and LoVo). Cell proliferation and invasion assays were conducted to investigate MARCHF9's functional relevance. Survival analyses were performed to assess its prognostic role. Results. Our analysis revealed significantly elevated MARCHF9 expression in CRC tissues compared to normal colorectal tissues (P < 0.05). High MARCHF9 expression correlated with advanced clinical stages, distant metastases, and the presence of residual tumors in CRC patients. Survival analyses demonstrated that high MARCHF9 expression predicted unfavorable overall and disease-free survival outcomes (P < 0.05). In vitro experiments further supported its oncogenic potential, with MARCHF9 knockdown inhibiting COAD cell proliferation and invasion. Conclusions. This study unveils the oncogenic role of MARCHF9 in CRC, highlighting its clinical relevance as a potential biomarker and therapeutic target. MARCHF9's association with adverse clinicopathological features and its functional impact on cancer cell behavior underscore its significance in CRC progression. Further research is essential to elucidate precise mechanisms by which MARCHF9 enhances tumorigenesis and to explore its therapeutic potential in CRC management.

Cereal-Derived Water-Unextractable Arabinoxylans: Structure Feature, Effects on Baking Products and Human Health.

Arabinoxylans (AXs) are non-starch polysaccharides with complex structures naturally occurring in grains (i.e., barley, corn, and others), providing many health benefits, especially as prebiotics. AXs can be classified as water-extractable (WEAX) and water-unextractable (WUAX) based on their solubility, with properties influenced by grain sources and extraction methods. Numerous studies show that AXs exert an important health impact, including glucose and lipid metabolism regulation and immune system enhancement, which is induced by the interactions between AXs and the gut microbiota. Recent research underscores the dependence of AX physiological effects on structure, advocating for a deeper understanding of structure-activity relationships. While systematic studies on WEAX are prevalent, knowledge gaps persist regarding WUAX, despite its higher grain abundance. Thus, this review reports recent data on WUAX structural properties (chemical structure, branching, and MW) in cereals under different treatments. It discusses WUAX applications in baking and the benefits deriving from gut fermentation.

A nomogram based on dual-layer detector spectral computed tomography quantitative parameters and morphological quantitative indicator for distinguishing metastatic and nonmetastatic regional lymph nodes in pancreatic ductal adenocarcinoma.

Background: There is no unified scope for regional lymph node (LN) dissection in patients with pancreatic ductal adenocarcinoma (PDAC). Incomplete regional LN dissection can lead to postoperative recurrence, while blind expansion of the scope of regional LN dissection significantly increases the perioperative risk without significantly prolonging overall survival. We aimed to establish a noninvasive visualization tool based on dual-layer detector spectral computed tomography (DLCT) to predict the probability of regional LN metastasis in patients with PDAC. Methods: A total of 163 regional LNs were reviewed and divided into a metastatic cohort (n=58 LNs) and nonmetastatic cohort (n=105 LNs). The DLCT quantitative parameters and the nodal ratio of the longest axis to the shortest axis (L/S) of the regional LNs were compared between the two cohorts. The DLCT quantitative parameters included the iodine concentration in the arterial phase (APIC), normalized iodine concentration in the arterial phase (APNIC), effective atomic number in the arterial phase (APZeff), normalized effective atomic number in the arterial phase (APNZeff), slope of the spectral attenuation curves in the arterial phase (APλHU), iodine concentration in the portal venous phase (PVPIC), normalized iodine concentration in the portal venous phase (PVPNIC), effective atomic number in the portal venous phase (PVPZeff), normalized effective atomic number in the portal venous phase (PVPNZeff), and slope of the spectral attenuation curves in the portal venous phase (PVPλHU). Logistic regression analysis based on area under the curve (AUC) was used to analyze the diagnostic performance of significant DLCT quantitative parameters, L/S, and the models combining significant DLCT quantitative parameters and L/S. A nomogram based on the models with highest diagnostic performance was developed as a predictor. The goodness of fit and clinical applicability of the nomogram were assessed through calibration curve and decision curve analysis (DCA). Results: The combined model of APNIC + L/S (APNIC + L/S) had the highest diagnostic performance among all models, yielding an AUC, sensitivity, and specificity of 0.878 [95% confidence interval (CI): 0.825-0.931], 0.707, and 0.886, respectively. The calibration curve indicated that the APNIC-L/S nomogram had good agreement between the predicted probability and the actual probability. Meanwhile, the decision curve indicated that the APNIC-L/S nomogram could produce a greater net benefit than could the all- or-no-intervention strategy, with threshold probabilities ranging from 0.0 to 0.75. Conclusions: As a valid and visual noninvasive prediction tool, the APNIC-L/S nomogram demonstrated favorable predictive efficacy for identifying metastatic LNs in patients with PDAC.

Differentiation of benign and malignant lesions in Bethesda III and IV thyroid nodules via dual-energy computed tomography quantitative parameters and morphologic features.

Background: Thyroid nodules (TNs) cytologically defined as category Bethesda III and IV pose a major diagnostic challenge before surgery, demanding new methods to reduce unnecessary diagnostic thyroid lobectomies for patients with benign TNs. This study aimed to assess whether a model combining dual-energy computed tomography (DECT) quantitative parameters with morphologic features could reliably differentiate between benign and malignant lesions in Bethesda III and IV TNs. Methods: Data from 77 patients scheduled for thyroid surgery for Bethesda III and IV TNs (malignant =48; benign =29) who underwent DECT scans were reviewed. DECT quantitative parameters including normalized iodine concentration (NIC), attenuation on the slope of spectral Hounsfield unit (HU) curve, and normalized effective atomic number (Zeff) were measured in the arterial phase (AP) and venous phase (VP). DECT quantitative parameters and morphologic features were compared between the malignant and benign cohorts. The receiver operating characteristic curve was performed to compare the performances of significant DECT quantitative parameters, morphologic features, or the models combining the DECT parameters, respectively, with morphologic features. A nomogram was constructed from the optimal performance model, and the performance was evaluated via the calibration curve and decision curve analysis. Results: The areas under the receiver operating characteristic curve with 95% confidence interval (CI) of the NIC in the AP (AP-NIC), slope of spectral HU curve in the AP, and NZeff in the AP were 0.749 (95% CI: 0.641-0.857), 0.654 (95% CI: 0.530-0.778), and 0.722 (95% CI: 0.602-0.842), respectively. The model combining AP-NIC with enhanced blurring showed the highest diagnostic performance, with an area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of 0.808, 0.854, and 0.655, respectively; it was then used to construct a nomogram. The calibration curve showed that the discrepancy between the prediction of the nomogram and actual observations was less than 5%. The decision curve analysis indicated the nomogram had a positive net benefit in threshold risk ranges of 14% to 58% or 60% to 91% for malignant Bethesda III and IV TNs. Conclusions: The model combining AP-NIC with enhanced blurring could reliably differentiate between benign and malignant lesions in Bethesda III and IV TNs.

Nurse-Led Care at Home Visit Versus Standard Care in Patients with Mild Acute Pancreatitis: A Retrospective Analysis.

BACKGROUNDS: Frequent hospitalization and the costs of hospitalization are the main burdens in China for patients with acute pancreatitis. Most admitted patients have mild disease conditions that do not require hospitalization. AIMS: Here, we compare some health and economic aspects of patients with mild acute pancreatitis who received nurse-led care at home visits against those who were hospitalized on follow-up. METHODS: Patients discharged from the hospital after treatment for mild acute pancreatitis received (NC cohort, n = 104) or did not receive (HN cohort, n = 141) regular home visits by nurses for treatment and care. Patients were rehospitalized by caregivers with or without help of nurse. RESULTS: Hospital readmission events occurred in both cohorts at a follow-up care time of 2 months. Compared with the time of discharge from the hospital, unwanted effects were higher in follow-up care in all patients (p < 0.001 for all). Patients in the NC cohort had less time to resolution of pain, less time to resumption of oral solid food intake, smaller number of patients with hospital readmissions, less average time of hospitalization, lower cost of care, and lower occurrence of unwanted effects than those of patients in the HN cohort during 2 months of follow-up care (p < 0.05 for all). CONCLUSIONS: Patients with mild acute pancreatitis who undergo treatment require nurse-led nontreatment intervention(s) for rehabilitation in follow-up. Nurse-led follow-up care at-home visits increase recovery, are beneficial and cost-effective, and decrease unwanted adverse effects in patients receiving treatment for mild acute pancreatitis. LEVEL OF EVIDENCE: IV. TECHNICAL EFFICACY: Stage 5.

Detection of malignant lesions in cytologically indeterminate thyroid nodules using a dual-layer spectral detector CT-clinical nomogram.

Purpose: To evaluate the capability of dual-layer detector spectral CT (DLCT) quantitative parameters in conjunction with clinical variables to detect malignant lesions in cytologically indeterminate thyroid nodules (TNs). Materials and methods: Data from 107 patients with cytologically indeterminate TNs who underwent DLCT scans were retrospectively reviewed and randomly divided into training and validation sets (7:3 ratio). DLCT quantitative parameters (iodine concentration (IC), NICP (IC nodule/IC thyroid parenchyma), NICA (IC nodule/IC ipsilateral carotid artery), attenuation on the slope of spectral HU curve and effective atomic number), along with clinical variables, were compared between benign and malignant cohorts through univariate analysis. Multivariable logistic regression analysis was employed to identify independent predictors which were used to construct the clinical model, DLCT model, and combined model. A nomogram was formulated based on optimal performing model, and its performance was assessed using receiver operating characteristic curve, calibration curve, and decision curve analysis. The nomogram was subsequently tested in the validation set. Results: Independent predictors associated with malignant TNs with indeterminate cytology included NICP in the arterial phase, Hashimoto's Thyroiditis (HT), and BRAF V600E (all p < 0.05). The DLCT-clinical nomogram, incorporating the aforementioned variables, exhibited superior performance than the clinical model or DLCT model in both training set (AUC: 0.875 vs 0.792 vs 0.824) and validation set (AUC: 0.874 vs 0.792 vs 0.779). The DLCT-clinical nomogram demonstrated satisfactory calibration and clinical utility in both training set and validation set. Conclusion: The DLCT-clinical nomogram emerges as an effective tool to detect malignant lesions in cytologically indeterminate TNs.

Enhancing traumatic brain injury emergency care: the impact of grading and zoning nursing management.

OBJECTIVE: This research aimed to evaluate the impact of grading and zoning nursing management on traumatic brain injury (TBI) patients' emergency treatment outcomes. METHODS: This randomized controlled trial included 200 TBI patients. They were treated with a conventional care (control group, n = 100) and a novel grading and zoning approach (study group, n = 100), respectively. This innovative model organized care into levels based on urgency and complexity, facilitating targeted medical response and resource allocation. Key metrics compared included demographic profiles, consultation efficiency (time metrics and emergency treatment rates), physiological parameters (HR, RR, MAP, SpO2, RBS), and patient outcomes (hospital and ICU stays, complication rates, and emergency outcomes). RESULTS: The study group demonstrated significantly improved consultation efficiency, with reduced times for physician visits, examinations, emergency stays, and specialist referrals (all p < 0.001), alongside a higher emergency treatment rate (93% vs. 79%, p = 0.004), notably better physiological stability, improved HR, RR, MAP, SpO2 and RBS (p < 0.001), shorter hospital and ICU stays, fewer complications, and superior emergency outcomes. CONCLUSION: Grading and zoning nursing management substantially enhances TBI patients' emergency care efficiency and clinical outcomes, suggesting a viable model for improving emergency treatment protocols.

TomoNet: A streamlined cryogenic electron tomography software pipeline with automatic particle picking on flexible lattices.

Cryogenic electron tomography (cryoET) is capable of determining in situ biological structures of molecular complexes at near-atomic resolution by averaging half a million subtomograms. While abundant complexes/particles are often clustered in arrays, precisely locating and seamlessly averaging such particles across many tomograms present major challenges. Here, we developed TomoNet, a software package with a modern graphical user interface to carry out the entire pipeline of cryoET and subtomogram averaging to achieve high resolution. TomoNet features built-in automatic particle picking and three-dimensional (3D) classification functions and integrates commonly used packages to streamline high-resolution subtomogram averaging for structures in 1D, 2D, or 3D arrays. Automatic particle picking is accomplished in two complementary ways: one based on template matching and the other using deep learning. TomoNet's hierarchical file organization and visual display facilitate efficient data management as required for large cryoET datasets. Applications of TomoNet to three types of datasets demonstrate its capability of efficient and accurate particle picking on flexible and imperfect lattices to obtain high-resolution 3D biological structures: virus-like particles, bacterial surface layers within cellular lamellae, and membranes decorated with nuclear egress protein complexes. These results demonstrate TomoNet's potential for broad applications to various cryoET projects targeting high-resolution in situ structures.

Immune cell trafficking: a novel perspective on the gut-skin axis.

Immune cell trafficking, an essential mechanism for maintaining immunological homeostasis and mounting effective responses to infections, operates under a stringent regulatory framework. Recent advances have shed light on the perturbation of cell migration patterns, highlighting how such disturbances can propagate inflammatory diseases from their origin to distal organs. This review collates and discusses current evidence that demonstrates atypical communication between the gut and skin, which are conventionally viewed as distinct immunological spheres, in the milieu of inflammation. We focus on the aberrant, reciprocal translocation of immune cells along the gut-skin axis as a pivotal factor linking intestinal and dermatological inflammatory conditions. Recognizing that the translation of these findings into clinical practices is nascent, we suggest that therapeutic strategies aimed at modulating the axis may offer substantial benefits in mitigating the widespread impact of inflammatory diseases.

TomoNet: A streamlined cryoET software pipeline with automatic particle picking on flexible lattices.

Cryogenic electron tomography (cryoET) is capable of determining in situ biological structures of molecular complexes at near atomic resolution by averaging half a million subtomograms. While abundant complexes/particles are often clustered in arrays, precisely locating and seamlessly averaging such particles across many tomograms present major challenges. Here, we developed TomoNet, a software package with a modern graphical user interface to carry out the entire pipeline of cryoET and subtomogram averaging to achieve high resolution. TomoNet features built-in automatic particle picking and 3D classification functions and integrates commonly used packages to streamline high-resolution subtomogram averaging for structures in one-, two- or three-dimensional arrays. Automatic particle picking is accomplished in two complementary ways: one based on template matching and the other employing deep learning. TomoNet's hierarchical file organization and visual display facilitate efficient data management as required for large cryoET datasets. Applications of TomoNet to three types of datasets demonstrate its capability of efficient and accurate particle picking on flexible and imperfect lattices to obtain high-resolution 3D biological structures: virus-like particles, bacterial surface layers within cellular lamellae, and membranes decorated with nuclear egress protein complexes. These results demonstrate TomoNet's potential for broad applications to various cryoET projects targeting high-resolution in situ structures.

Amelioration of nitroglycerin-induced migraine in mice via Wuzhuyu decoction: Inhibition of the MZF1/PGK1 pathway and activation of NRF2 antioxidant response.

ETHNOPHARMACOLOGICAL RELEVANCE: Migraine, a chronic and intricate disorder, manifests as recurrent episodic headaches accompanied by various neurological symptoms. Wuzhuyu Decoction (WZYD) is a traditional Chinese medical formula with promising effects in treating migraines; however, its underlying mechanisms have not yet been clarified. AIM OF STUDY: The study aimed to evaluate WZYD's effectiveness in migraine treatment and investigate the potential mechanism of WZYD's effects on migraine and oxidative stress. MATERIALS AND METHODS: Behavior tests and immunofluorescence assay for the intensity of migraine markers to assess the migraine-relieving effect of WZYD after chronic migraine model induced by nitroglycerin in mice. The impacts of WZYD on oxidative stress-related markers, including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO1), and NAD (P)H quinone oxidoreductase 1 (NQO1) in brain tissue were examined. In addition, protein expression or mRNA levels of the MZF1/PGK1 were detected using Western blot or PCR, respectively. Finally, the MZF1 overexpression vector was constructed to the higher level of MZF1. The MZF1/PGK1 signaling pathway expression was evaluated by markers of oxidative stress including NRF2 and others in this series of experiments. RESULTS: Through murine model experimentation, we observed that WZYD effectively alleviates migraine symptoms, signifying its therapeutic efficacy. Mechanistically, WZYD emerges as a potent activator of the NRF2, acting as a robust defense against oxidative stress. In vitro investigations demonstrated that WZYD combats oxidative stress and curbs cell apoptosis induced by these detrimental conditions. Furthermore, by suppressing the transcriptional expression of PGK1, an influential player in the NRF2 pathway, WZYD effectively activates NRF2 signaling. Intriguingly, we have identified MZF1 as the mediator orchestrating the regulation of the PGK1/NRF2 pathway by WZYD. CONCLUSION: The study confirms the effectiveness of WZYD in alleviating migraine symptoms. Mechanistically, WZYD activated the NRF2 signaling pathway; moreover, the action of WZYD involved the down-regulation of PGK1 mediated by MZF1, which promoted the activation of the NRF2 pathway. This study advances our understanding of the intricate mechanisms driving WZYD's efficacy, paving the way for novel treatments in migraine management.

Substrate-free dissolving microneedles with barbed shape to increase adhesion and drug-delivery efficiency to skin.

Microneedle drug delivery has recently emerged as a clinical method, and dissolving microneedles (DMNs) offer exclusive simplicity and efficiency, compared to the other kinds of microneedles. The tips of most currently available DMNs are cone/house-shaped to result in a lower penetration force. Penetration of the needle tips into the skin relies mainly on the back tape or external pressure, and their adhesion to the skin is relatively low. In addition, only the drug in the part of tips that are pierced into the dermis can be dissolved, resulting in drug waste. Inspired from the barbed structure of the honeybee stinger, we reported substrate-free DMNs with a barbed structure by a dual-molding process, which is suitable for mass production. Those DMNs showed 3-fold greater adhesion force between the needle tips and the skin, better dissolution and deeper penetration than house-shaped DMNs in vivo under the same conditions. For the in situ treatment of psoriasis in mice, the barbed DMNs required only the half dose of house-shaped DMNs to achieve similar efficacy.

Development and validation of a model for predicting the expression of Ki-67 in pancreatic ductal adenocarcinoma with radiological features and dual-energy computed tomography quantitative parameters.

OBJECTIVE: To construct and validate a model based on the dual-energy computed tomography (DECT) quantitative parameters and radiological features to predict Ki-67 expression levels in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Data from 143 PDAC patients were analysed. The variables of clinic, radiology and DECT were evaluated. In the arterial phase and portal venous phase (PVP), the normalized iodine concentration (NIC), normalized effective atomic number and slope of the spectral attenuation curves were measured. The extracellular volume fraction (ECVf) was measured in the equilibrium phase. Univariate analysis was used to screen independent risk factors to predict Ki-67 expression. The Radiology, DECT and DECT-Radiology models were constructed, and their diagnostic effectiveness and clinical applicability were obtained through area under the curve (AUC) and decision curve analysis, respectively. The nomogram was established based on the optimal model, and its goodness-of-fit was assessed by a calibration curve. RESULTS: Computed tomography reported regional lymph node status, NIC of PVP, and ECVf were independent predictors for Ki-67 expression prediction. The AUCs of the Radiology, DECT, and DECT-Radiology models were 0.705, 0.884, and 0.905, respectively, in the training cohort, and 0.669, 0.835, and 0.865, respectively, in the validation cohort. The DECT-Radiology nomogram was established based on the DECT-Radiology model, which showed the highest net benefit and satisfactory consistency. CONCLUSIONS: The DECT-Radiology model shows favourable predictive efficacy for Ki-67 expression, which may be of value for clinical decision-making in PDAC patients. CRITICAL RELEVANCE STATEMENT: The DECT-Radiology model could contribute to the preoperative and non-invasive assessment of Ki-67 expression of PDAC, which may help clinicians to screen out PDAC patients with high Ki-67 expression. KEY POINTS: • Dual-energy computed tomography (DECT) can predict Ki-67 in pancreatic ductal adenocarcinoma (PDAC). • The DECT-Radiology model facilitates preoperative and non-invasive assessment of PDAC Ki-67 expression. • The nomogram may help screen out PDAC patients with high Ki-67 expression.

Effects of Lactiplantibacillus plantarum dy-1 fermentation on multi-scale structure and physicochemical properties of barley starch.

The effects of fermentation on barley starch were studied using Lactiplantibacillus plantarum dy-1. Changes in multi-scale structure and physicochemical properties of barley starch were studied. The chain structure results revealed that fermentation could increase the content of short chain and medium short chain by breaking down long amylopectin side chains in barley and increase amylose content by debranching amylopectin. Also, fermentation promoted the arrangement of short chains into short order structure, leading to the enhancement of hydrogen bond interaction. Furthermore, it improved the helical structure content and relative crystallinity of barley starch by degrading the amorphous structure of barley starch. In terms of physicochemical properties, fermentation inhibited the hydration characteristics of barley starch, thus improving its thermal stability. It also enhanced shear stability, resistance to short-term aging and digestion, and improved gel texture properties. These findings offer potential for the processing and nutritional regulation of fermented barley products.

Wireless facial biosensing system for monitoring facial palsy with flexible microneedle electrode arrays.

Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device's soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.

Hierarchical organization and assembly of the archaeal cell sheath from an amyloid-like protein.

Certain archaeal cells possess external proteinaceous sheath, whose structure and organization are both unknown. By cellular cryogenic electron tomography (cryoET), here we have determined sheath organization of the prototypical archaeon, Methanospirillum hungatei. Fitting of Alphafold-predicted model of the sheath protein (SH) monomer into the 7.9 Å-resolution structure reveals that the sheath cylinder consists of axially stacked ß-hoops, each of which is comprised of two to six 400 nm-diameter rings of ß-strand arches (ß-rings). With both similarities to and differences from amyloid cross-ß fibril architecture, each ß-ring contains two giant ß-sheets contributed by ~ 450 SH monomers that entirely encircle the outer circumference of the cell. Tomograms of immature cells suggest models of sheath biogenesis: oligomerization of SH monomers into ß-ring precursors after their membrane-proximal cytoplasmic synthesis, followed by translocation through the unplugged end of a dividing cell, and insertion of nascent ß-hoops into the immature sheath cylinder at the junction of two daughter cells.

Metabolomics reveals the effects of Lactiplantibacillus plantarum dy-1 fermentation on the lipid-lowering capacity of barley ß-glucans in an in vitro model of gut-liver axis.

Bioactive polysaccharides known as the biological response modifiers, can directly interact with intestinal epithelium cells (IEC) and regulate key metabolic processes such as lipid metabolism. Here, the coculture of Caco-2/HT29 monolayer (>400 Ω × cm2) and HepG2 cells was developed to mimic the gut-liver interactions. This system was used to investigate the effects of raw and fermented barley ß-glucans (RBG and FBG) on lipid metabolism by directly interacting with IEC. Both RBG and FBG significantly and consistently reduced the lipid droplets and triacylglycerol levels in monoculture and coculture of HepG2 overloaded with oleic acid. Notably, FBG significantly and distinctly elevated PPARα (p < 0.05) and PPARα-responsive ACOX-1 (p < 0.01) gene expressions, promoting lipid degradation in cocultured HepG2. Moreover, the metabolomics analyses revealed that FBG had a unique impact on extracellular metabolites, among them, the differential metabolite thiomorpholine 3-carboxylate was significantly and strongly correlated with PPARα (r = -0.68, p < 0.01) and ACOX-1 (r = -0.76, p < 0.01) expression levels. Taken together, our findings suggest that FBG-mediated gut-liver interactions play a key role in its lipid-lowering effects that are superior to those of RBG. These results support the application of Lactiplantibacillus fermentation for improving hypolipidemic outcomes.